Skip to main content Accessibility help
Hostname: page-component-6f6fcd54b-n4hhg Total loading time: 0.34 Render date: 2021-05-11T14:57:33.277Z Has data issue: true Feature Flags: {}

Authors' reply

Published online by Cambridge University Press:  02 January 2018

Michael J. Peluso
Yale School of Medicine, Harkness Hill, ESH 219, 367 Cedar Street, New Haven, CT 06510, USA. Email:
Shôn W. Lewis
University of Manchester
Thomas R. E. Barnes
Centre for Mental Health, Imperial College London
Peter B. Jones
Department of Psychiatry, University of Cambridge, and Early Intervention Services for Cambridgeshire & Peterborough NHS Foundation Trust (CAMEO), UK
E-mail address:
Rights & Permissions[Opens in a new window]


Copyright © Royal College of Psychiatrists, 2012 

We thank Dr Temmingh for his interest in our paper. Reference Peluso, Lewis, Barnes and Jones1 The use of sulpiride in CUtLASS-1 was discussed in the original report Reference Jones, Barnes, Davies, Dunn, Lloyd and Hayhurst2 and subsequent correspondence. Reference Jones, Barnes, Elton, Davies, Dunn and Lloyd3 The Cochrane review of sulpiride in schizophrenia Reference Soares, Fenton and Chue4 concluded that extrapyramidal side-effects (EPS) may be less frequent for individuals taking sulpiride but that no result regarding either direct or proxy measures of EPS reached statistical significance. Moreover, the review includes a report that sulpiride seemed to cause problems with increased prolactin levels and galactorrhoea. Reference Weizman, Maoz, Treves, Asher and Ben David5 Claims that the drug shows particular efficacy against negative symptoms were not supported by trial data. Thus, any evidence that sulpiride is a particularly atypical typical antipsychotic is, at best, not strong. It is similar to amisulpride in its chemical structure and receptor pharmacology, with highly selective affinity for pre- and post-synaptic D2 and D3 receptors, Reference Schoemaker, Claustre, Fage, Rouquier, Chergui and Curet6 characteristics of both drugs that question the validity of the typical v. atypical classification.

We acknowledge in the paper Reference Peluso, Lewis, Barnes and Jones1 that a cautious approach is needed when undertaking a secondary analysis of any trial data because sample size will have been predicated on the primary, not secondary, hypothesis, and because many hypothesis tests may be undertaken; type 1 and 2 statistical errors lie in wait even for a Cochrane review. That is why we defined a doubling or halving of EPS as a clinically meaningful effect size to use in conjunction with significance testing. This was a matter of clinical judgement rather than being completely arbitrary. Like the conventional 5% cut-off used in significance testing, we hope it has some value while acknowledging that all these decisions are subject to controversy. Reference Glaser7 In deciding to dichotomise EPS in this way, we were aiming to keep things simple and avoid erroneous conclusions from multiple secondary analyses.

We agree that the findings raise important points for the design of superiority (and non-inferiority) trials, and for crucial policy decisions based on health economic evidence. However, we hope that the findings may also remind clinicians that older antipsychotic drugs may be worth a thought when trying to find the right medicine for a particular patient.


Declaration of interest

In the past 3 years, S.W.L. has received advisory board fees from Janssen-Cilag and speaker fees from AstraZeneca; T.R.E.B. has spoken at an event sponsored by Lilly; P.B.J. is a member of a scientific advisory board for Roche, and has received research support from GlaxoSmithKline and a speaker fee from Lilly.


1 Peluso, MJ, Lewis, SW, Barnes, TRE, Jones, PB. Extrapyramidal motor side–effects of first–and second-generation antipsychotic drugs. Br J Psychiatry 2012; 200: 387–92.CrossRefGoogle ScholarPubMed
2 Jones, PB, Barnes, TR, Davies, L, Dunn, G, Lloyd, H, Hayhurst, KP, et al. Randomized controlled trial of the effect on Quality of Life of second– vs first–generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079–87.CrossRefGoogle Scholar
3 Jones, PB, Barnes, TRE, Elton, P, Davies, L, Dunn, G, Lloyd, H, et al. First– vs second–generation antipsychotic drugs in schizophrenia - reply. Arch Gen Psychiatry 2007; 64: 979–80.CrossRefGoogle Scholar
4 Soares, BG, Fenton, M, Chue, P. Sulpiride for schizophrenia. Cochrane Database Syst Rev 2000; 2: CD001162.Google Scholar
5 Weizman, A, Maoz, B, Treves, I, Asher, I, Ben David, M. Sulpiride–induced hyperprolactinemia and impotence in male psychiatric outpatients. Prog Neuropsychopharmacology Biol Psychiatry 1985; 9: 193–8.CrossRefGoogle ScholarPubMed
6 Schoemaker, H, Claustre, Y, Fage, D, Rouquier, L, Chergui, K, Curet, O, et al. Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther 1997; 280: 183–97.Google ScholarPubMed
7 Glaser, DN. The controversy of significance testing: misconceptions and alternatives. Am J Crit Care 1999; 8: 291–6.Google ScholarPubMed
Submit a response


No eLetters have been published for this article.
You have Access

Send article to Kindle

To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Authors' reply
Available formats

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Authors' reply
Available formats

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Authors' reply
Available formats

Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *