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, C. B. Nemeroff, A. F. Schatzberg, T. Schlaepfer, A. McConnachie, L. Haazen, E. Buntinx

Research output: Contribution to journalArticle

11 Scopus citations


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 (US)
Pages (from-to)2089-2097
Number of pages9
JournalPsychological medicine
Issue number10
StatePublished - Oct 1 2011



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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology

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