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-HT 2A receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT 2A /D 4 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.

Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs

“…Furthermore, cariprazine, a DA D 2 , DA D 3 and 5-HT 1A receptor partial agonist [32], is currently undergoing clinical testing as adjunctive treatment for MDD [33]. On the other hand, PNB-01, a combination of citalopram and a low dose of pipamperone (D 2 , D 4 and 5-HT 2A receptor antagonist), has failed to show any advantages over the treatment with citalopram alone in one clinical study [34]. A follow-up phase 3 study has been registered at http://clinicaltrials.gov, but patients have not yet been recruited (https://clinicaltrials.gov/show/ NCT01312922).…”

Evaluation of a Predictive Algorithm that Detects Aberrant Use of Opioids in an Addiction Treatment Centre

“…Fisher's exact test was performed to determine any differences in gender. A cross-tab analysis was performed to assess the diagnostic Alcohol and Drug Abuse [25,26] Anxiety [27] Depression [28] Dopamine BetaHydroxylase DBH rs1611115…”

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“…In a randomized, multicenter, placebo-controlled trial, a dose of pipamperone probably blocking no more than ∼60% of brain 5-HT 2A receptors appeared to exert an antidepressant effect when added onto citalopram, especially during treatment weeks 1-4 (Wade et al, 2011). However, the common pharmacological action shared by approved antidepressants trazodone (2-[3-[4-(3-chlorophenyl) .…”