Improvement in symptoms of depression is typically delayed with antidepressant treatment. Pipamperone (PIP) at low doses acts as a highly selective 5HT2A/D4 receptor antagonist. The purpose of this study was to investigate whether the addition of PIP to the SSRI citalopram (CIT) would increase the rate of resolution of depressive symptoms.

This was an 8-week, double-blind, parallel-group, single-dummy study in patients with MDD who received either CIT 40 mg daily or PIP 5 mg bid plus CIT 40 mg daily (PIPCIT).

The mean total MADRS score (±SD) of the 165 patients (81% women; mean age, 40 y) was 32.6±5.5. More CIT than PIPCIT patients discontinued treatment in the first 4 weeks [15 (18%) vs 3 (4%); P=0.003]. Reductions in mean total MADRS scores were significantly (ITT LOCF) larger in patients receiving PIPCIT after 1 week [-6.42±6.18 vs -3.99±5.15; P=0.007] and 4 weeks [-15.06±8.48 vs - 12.11±8.30; P=0.025] compared with those receiving CIT alone. Significant differences in favor of PIPCIT were observed in MADRS items “reduced sleep,” “reduced appetite,” “concentration difficulties,” and “pessimistic thoughts.” Mean CGI-I scores were also improved after 1 week of PIPCIT [3.09±0.85 vs. 3.47±0.72; P=0.002]. There were no significant differences observed at 8 weeks. No additional, clinically significant adverse events were noted in the PIPCIT group.

A low dose of PIP added to CIT provided superior antidepressant effects and less discontinuations compared with CIT alone during the first 4 weeks of treatment, and especially in the first week, at apparently no tolerability/safety cost.