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.

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.

• Authors: A G Wade, G M Crawford, C B Nemeroff, A F Schatzberg, T Schlaepfer, A McConnachie, L Haazen, E Buntinx
• Journal: Psychological medicine (Psychol Med) Vol. 41 Issue 10 Pg. 2089-97 (Oct 2011) ISSN: 1469-8978 [Electronic] England
• PMID: 21349239 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Butyrophenones
• Placebos
• Serotonin Antagonists
• Serotonin Uptake Inhibitors
• Citalopram
• pipamperone

Topics

• Adolescent
• Adult
• Aged
• Butyrophenones (administration & dosage, adverse effects, standards, therapeutic use)
• Citalopram (administration & dosage, adverse effects, standards, therapeutic use)
• Depressive Disorder, Major (diagnosis, drug therapy)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Male
• Middle Aged
• Placebos
• Psychiatric Status Rating Scales
• Scotland
• Serotonin Antagonists (administration & dosage, adverse effects, standards, therapeutic use)
• Selective Serotonin Reuptake Inhibitors (administration & dosage, adverse effects, standards, therapeutic use)
• Treatment Outcome
• Young Adult