Low dose pipamperone therapy for major depression: A randomized controlled clinical trial comparison with citalopram

Abstract

Objective

Serotonin-Dopamine antagonists (SDA) have been evaluated as monotherapy and augmentation therapy for major depression (MDD) Despite evidence of efficacy for both, adverse events with SDA are considerably greater than for monotherapy. In this randomized clinical trial, low doses of pipamperone, an SDA approved in the EU, were used to treat major depression. We were in efficacy across treatments and the relative safety of pipamperone compared to previous treatments with SDA.

Methods

In this study, patients with MDD (n = 555; 535 received treatment) were randomized to low dose pipamperone plus placebo, citalopram plus placebo, or pipamperone plus citalopram in a 10-week efficacy study. Adverse events and clinician efficacy ratings with MADRS were examined.

Results

The study was completed by 383 participants, with the most common reason for drop out being withdrawal of consent. All three arms showed treatment-related changes with no significant differences between treatments (all effect sizes from larger than d = 1.48, largest = 1.77: pipamperone plus citalopram). Drop-outs due to adverse events were 4 % with pipamperone monotherapy, compared to 3 % with citalopram alone. There were no differences in weight gain across the treatments and EPS was reported by one case and tremor was reported by two cases with combined treatment arm. Nausea was more common with citalopram monotherapy (16 % vs 9 % for pipamperone).

Conclusions

These data suggest that low doses of pipamperone have a substantially better safety profile than previous SDA medications used to treat MDD and that pipamperone has potential to be an efficacious treatment for MD, as monotherapy or combination therapy.

Clinical Trials Registration

This trial was registered on clinicaltrials.gov: (NCT01312922).