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Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response

Published online by Cambridge University Press:  25 February 2011

A. G. Wade ,
G. M. Crawford ,
C. B. Nemeroff ,
A. F. Schatzberg ,
T. Schlaepfer ,
A. McConnachie ,
L. Haazen  and
E. Buntinx
A. G. Wade*
Affiliation:
CPS Research, Glasgow, Scotland, UK
G. M. Crawford
Affiliation:
CPS Research, Glasgow, Scotland, UK
C. B. Nemeroff
Affiliation:
Department of Psychiatry and Behavioral Sciences, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA
A. F. Schatzberg
Affiliation:
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
T. Schlaepfer
Affiliation:
Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Psychiatry and Psychotherapy, University of Bonn, Germany
A. McConnachie
Affiliation:
Robertson Centre for Biostatistics, University of Glasgow, Scotland, UK
L. Haazen
Affiliation:
PharmaNeuroBoost NV, Alken, Belgium
E. Buntinx
Affiliation:
PharmaNeuroBoost NV, Alken, Belgium
*
*Address for correspondence: A. G. Wade, CPS Research, 3 Todd Campus, Glasgow G20 0XA, UK. (Email: [email protected])
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Abstract

Background

Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT2A/D4 antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect.

Method

An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out.

Results

The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (s.d.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002).

Conclusions

Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week.

Keywords

CitalopramdepressionMontgomery–Asberg Depression Rating Scalepipamperoneselective serotonin reuptake inhibitors
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 10 , October 2011 , pp. 2089 - 2097
Copyright
Copyright © Cambridge University Press 2011

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