title: 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.
  
  
  METHODS
  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.affiliation: CPS Research, Glasgow, Scotland, UK. alangwade@fastmail.fm
authors.forename: A G
authors.initials: AG
authors.lastname: Wade
authors.forename: G M
authors.initials: GM
authors.lastname: Crawford
authors.forename: C B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: A F
authors.initials: AF
authors.lastname: Schatzberg
authors.forename: T
authors.initials: T
authors.lastname: Schlaepfer
authors.forename: A
authors.initials: A
authors.lastname: McConnachie
authors.forename: L
authors.initials: L
authors.lastname: Haazen
authors.forename: E
authors.initials: E
authors.lastname: Buntinx
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002090:Butyrophenones / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012606:Scotland; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002090:Butyrophenones; D015283:Citalopram; D010919:Placebos; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C005569:pipamperone