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.
Author(s): Wade AG, Crawford GM, Nemeroff CB, Schatzberg AF, Schlaepfer T, McConnachie A,
Haazen L, Buntinx E.
Affiliation(s): CPS Research, Glasgow, Scotland, UK. alangwade@fastmail.fm
Publication date & source: 2011, Psychol Med. , 41(10):2089-97
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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