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

A. G. Wade, G. M. Crawford, Charles Nemeroff, A. F. Schatzberg, T. Schlaepfer, A. McConnachie, L. Haazen, E. Buntinx

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2089-2097
Number of pages9
JournalPsychological Medicine
Volume41
Issue number10
DOIs
StatePublished - Oct 1 2011

Fingerprint

pipamperone
Citalopram
Major Depressive Disorder
Double-Blind Method
Placebos
Depression
Observation
Therapeutic Uses
Antidepressive Agents
Serotonin 5-HT2 Receptor Antagonists
Receptor, Serotonin, 5-HT2A
Serotonin Uptake Inhibitors
Appetite
Sleep

Keywords

  • Citalopram
  • depression
  • Montgomery-Asberg Depression Rating Scale
  • pipamperone
  • selective serotonin reuptake inhibitors

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology

Cite this

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. / Wade, A. G.; Crawford, G. M.; Nemeroff, Charles; Schatzberg, A. F.; Schlaepfer, T.; McConnachie, A.; Haazen, L.; Buntinx, E.

In: Psychological Medicine, Vol. 41, No. 10, 01.10.2011, p. 2089-2097.

Research output: Contribution to journalArticle

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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.",
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AU - Crawford, G. M.

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