The British Journal of Psychiatry (2015)

207, 177178

Correspondence
Edited by Kiriakos Xenitidis and
Colin Campbell

Contents
&

Did you add the same study twice in the

meta-analysis?

&

Schizophrenia and mixed-handedness

Did you add the same study twice

in the meta-analysis?
I read with interest the systematic review of pharmacotherapy for
post-traumatic stress disorder (PTSD) by Mathew Hoskins and
colleagues. Looking at Fig. 2 of the paper and at the online-only
supplemental file, however, it seems to me that two unpublished
studies have been counted twice in the meta-analysis. As far as I
can see from the information reported in the review, the study
Eli Lilly is the same as Martenyi 2007 and Pfizer 589 is the
same as Friedman 2007 (same drugs, same comparisons, same
sample size). I would be grateful if the authors could clarify the
matter.
1

Authors reply: Professor Cipriani helpfully questions duplication

of data from two unpublished studies in our review. We could not
get access to the unpublished material for Eli Lilly and Pfizer
589, even after contacting the pharmaceutical companies, and
instead relied on the raw data sets obtained from previous reviews.
We have contacted Dr Friedman, who has confirmed that
Pfizer 589 was subsequently published as Friedman 2007. We
have also contacted the authors of Martenyi 2007, but are, as
yet, unable to confirm if this is the published Eli Lilly paper. This
seems distinctly possible, as the sample sizes are the same but it is
important to note that Eli Lilly only released Treatment Outcome
PTSD Scale data and not Clinician Administered PTSD Scale data
to the National Institute of Health and Care Excellence reviewers.
When the Pfizer 589 data are removed, it changes the outcome
for sertraline, which now demonstrates a small but statistically
significant advantage over placebo in reducing the severity of
clinician-rated PTSD symptoms (8 studies, n = 1271, SMD
70.16 (95%CI 70.31 to 70.02), w2 = 33%). This means that
paroxetine, fluoxetine, venlafaxine and sertraline can be considered
as potential treatments for PTSD.
The outcome for the trauma-type sub-analysis for sertraline is
still statistically insignificant (3 studies, n = 278, SMD 70.42
(95%CI 71.03 to 0.19), w2 = 81%). Eli Lilly was not included
in the meta-analysis of individual agents v. placebo. The overall
meta-analysis of selective serotonin-reuptake inhibitors (SSRIs)
v. placebo, when Eli Lilly and Pfizer 589 are removed, is now
slightly more in favour of SSRIs (19 studies, n = 3350, SMD
70.27 (95%CI 70.37 to 70.16), w2 = 45%); see revised forest
plot, here Fig. 1).

Hoskins M, Pearce J, Bethell A, Dankova L, Barbui C, Tol QA, et al.

Pharmacotherapy for post-traumatic stress disorder: systematic review
and meta-analysis. Br J Psychiatry 2015; 206: 93100.

Andrea Cipriani, Associate Professor, University of Oxford. Email:

andrea.cipriani@psych.ox.ac.uk

Mathew Hoskins, Jennifer Pearce, Andrew Bethell, Cardiff University, Cardiff,

UK; Corrado Barbui, University of Verona, Verona, Italy; Wietse A. Tol, Johns
Hopkins Bloomberg School of Public Health, Baltimore, USA; Soraya Seedat,
Stellenbosch University, Stellenbosch, South Africa; Hanhui Chen, Shanghai Jiaotong
University, Shanghai, China; Jonathan I. Bisson, Institute of Psychological Medicine
and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, UK. Email:
BissonJI@cardiff.ac.uk

doi: 10.1192/bjp.207.2.177

doi: 10.1192/bjp.207.2.177a

Study or subgroup
Brady (2000)38
Brady (2005)61
Connor (1999)40
DavidsonA
Davidson (2001)42
Friedman (2007)21
Hertzberg (2000)47
Marshall (2001)50
Marshall (2004)64
Martenyi (2002)51
Martenyi (2007)23
Panahi (2011)26
Pfizer 588C
Shaleve (2011)27
SKB627E
Tucker (2001)53
Tucker (2003)68
Van der Kolk (2007)70
Zohar (2002)54
Total (95% CI)

Experimental
Mean
s.d. Total
733
28.1
94
32.56 15.69
49
10.1
9.8
25
739.4 27.12 173
733
23.76 100
713.1 27.5
86
47
8
6
738.75 27.2
375
55.6 33.4
25
734.6 28.1
226
742.85 25.5
323
722.7
7.3
35
727.4 27.12
94
731.12 29.63
23
736.5 26.1
109
735.5 24.58 151
741.82 29.09
23
733.23 22.11
30
718.7
6.7
23

Mean
723.2
32.7
20.5
734.17
726.2
715.4
42
725.3
62.8
26.8
736.6
717.5
727.9
727.8
730.8
724.7
738.7
730.95
713.5

Control
s.d.
28.7
28.75
12.6
28.42
23.9
28.07
11
25.8
40.8
26.1
25.7
7.5
28.42
20.13
25.37
24.98
29.07
22.6
6.6

1968

Total
93
45
22
179
108
83
6
188
27
75
88
35
94
23
103
156
10
29
19
1382

Weight
5.8%
4.1%
2.4%
7.3%
6.1%
5.6%
0.8%
8.0%
2.8%
6.3%
6.8%
3.3%
5.9%
2.5%
6.2%
7.0%
1.7%
3.0%
2.2%

SMD IV, random, 95% CI

70.34 (70.63, 70.05)
70.01 (70.41, 0.40)
70.91 (71.52, 70.31) 8
70.19 (70.40, 0.02)
70.28 (70.56, 70.01)
0.08 (70.22, 0.38)
0.48 (70.68, 1.64)
70.50 (70.68, 70.32)
70.19 (70.73, 0.36)
70.28 (70.54, 70.02)
70.24 (70.48, 70.01)
70.69 (71.18, 70.21)
0.02 (70.27, 0.30)
70.13 (70.71, 0.45)
70.22 (70.49, 0.05)
70.43 (70.66, 70.21)
70.10 (70.85, 0.64)
70.10 (70.61, 0.41)
70.77 (71.40, 70.14) 8

100.0%

70.27 (70.37, 70.16)

SMD IV, random, 95% CI

Heterogeneity: t2 = 0.02; w2 = 32.43, d.f. = 18 (P = 0.02); I 2 = 45%

Test for overall effect: Z = 5.04 (P50.00001)
70.2

70.1

Favours experimental

Fig. 1

0.1

0.2

Favours control

Revised meta-analysis of selective serotonin reuptake inhibitors v. placebo (SMD, standardised mean difference).

177

Correspondence

Schizophrenia and mixed-handedness

1

The new meta-analysis by Hirnstein & Hugdahl shows that

schizophrenia is robustly associated with non-right-handedness
and thus makes a strong case for genetic links between schizophrenia, brain lateralisation and handedness. The association
was obtained meta-analytically for psychometrically assessed
handedness, and it was even stronger when handedness was
assessed behaviourally. Of interest, the available evidence also
allowed the tentative conclusion that this association might foremost be driven by mixed-handedness, rather than left-handedness,
thus suggesting that the strength of handedness, rather than its
direction, might actually be linked to schizophrenia.
With regard to this possibility, we emphasise that assessment
and classification reliability is a pervasive problem in handedness
research. Studies in this field often treat handedness as a binary
variable, comprising only right v. left preferences, and frequently
merely use single-item measures, or arbitrary criteria for
handedness classification, when multi-item inventories are used.
However, recent evidence2 shows that psychometrically
assessed handedness is in fact taxonic and discrete that is,
a matter of qualitative, rather than quantitative, differences
consisting of the taxa of right-, left- and mixed-handedness.
Similarly, psychometrically assessed footedness, earedness, and
eyedness all consist of these three taxa, which, together with
handedness, might be explained by underlying sidedness, which
also consists of the above three taxa. Further, handedness has been
found to be a biased indicator of mixed-sidedness, which might be
explained by ubiquitous external and societal pressures promoting
right-hand preference among actual non-right-handers.3 It
therefore appears that footedness, obviously being less influenced
by such external pressures, is the most important predictor of
sidedness.2
Given these facts, it is interesting to note that the Hirnstein &
Hugdahl meta-analysis was still able to hint at mixed-handedness
as the probable factor driving the association between

178

schizophrenia and non-right-handedness, thereby making a convincing case for the power of the meta-analytical approach, which,
through data aggregation, might overcome methodological
problems of individual studies. In addition, increasing the
classification reliability of handedness has recently aided in
clarifying the hypothesised seasonal pattern of birth months
among left-handed men,4 a hypothesis for which the available
previous evidence had been highly inconsistent.
We thus recommend utilising psychometrically validated scales,
along with a trichotomous classification, in investigations on
schizophrenia and handedness, expecting that mixed-handedness
might turn out to be more relevant than left-handedness for
explaining this link. Further, we recommend intensifying research
specifically with regard to footedness, which might be more
important with regard to brain lateralisation than handedness,5
and might provide more direct, and thus more robust, behavioural
evidence for the links between schizophrenia and brain
lateralisation.
1

Hirnstein M, Hugdahl K. Excess of non-right-handedness in schizophrenia:

meta-analysis of gender effects and potential biases in handedness
assessment. Br J Psychiatry 2014; 205: 2607.

Tran US, Stieger S, Voracek M. Evidence for general right-, mixed-, and leftsidedness in self-reported handedness, footedness, eyedness, and
earedness, and a primacy of footedness in a large-sample latent variable
analysis. Neuropsychologia 2014; 62: 22032.

Porac C, Coren S. Lateral Preferences and Human Behavior. Springer, 1981.

Tran US, Stieger S, Voracek M. Latent variable analysis indicates that

seasonal anisotropy accounts for the higher prevalence of left-handedness in
men. Cortex 2014; 57: 18897.

Elias LJ, Bryden MP. Footedness is a better predictor of language

lateralisation than handedness. Laterality 1998; 3: 4151.

Ulrich S. Tran, Martin Voracek, Department of Basic Psychological Research

and Research Methods, School of Psychology, University of Vienna, Vienna, Austria.
Email: ulrich.tran@univie.ac.at
doi: 10.1192/bjp.207.2.178