A short-term double-blind randomized controlled pilot trial with active or placebo pindolol in patients treated with venlafaxine for major depression

Abstract

Background: Pindolol has been widely investigated as an augmenter of antidepressant drug response. Results have been inconsistent. In this study, we used pindolol together with venlafaxine because of its ability to achieve a rapid onset of serotonin transporter blockade. Aims: The object of this study was thus to investigate if pindolol augments the antidepressant response to venlafaxine. Methods: Patients with major depression were randomized to either active or placebo pindolol 20 mg retard daily dosage and concomitantly treated with venlafaxine for 19 days. Depression severity was evaluated at four visits. Plasma concentrations of venlafaxine and its major metabolites O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) and pindolol were analysed. The ratio of ODV/venlafaxine was calculated. A low ratio corresponds to patients being poor metabolizers and a high ratio corresponds to patients being extensive metabolizers. Results: No statistically significant difference in depression outcome was found between treatment groups. A statistically significant effect was, however, found of the ratio of ODV/venlafaxine on depression outcome, showing an augmenting effect of pindolol in patients with a low ratio, and the reverse in patients with a high ratio. Conclusion: The differential effect of pindolol, on depression outcome, in patients with varying degrees of venlafaxine metabolism into ODV, corresponds to patients being poor or extensive metabolizers of venlafaxine. From this finding, we conclude that only patients who are poor metabolizers of venlafaxine might benefit from pindolol augmentation. This mechanism might explain some of the variability of outcome in pindolol augmentation studies.

• Depressive disorder
• Drug monitoring
• Pindolol
• Randomized controlled trial
• Venlafaxine

Acknowledgements

None.

Conflicts of interest: Dr Klaus Martiny has occasionally over the past 3 years been a speaker for pharmaceutical companies with an interest in the drug treatment of affective disorders (Lilly, Organon, Boehringer Ingelheim and Servier). Dr Martiny reported no other financial interests or potential conflicts of interest. Marianne Lunde reported no financial interests or potential conflicts of interest. Until August 2008, Professor Per Bech occasionally received funding from and was a speaker or member of advisory boards for pharmaceutical companies with an interest in the drug treatment of affective disorders (Astra-Zeneca, Lilly, H Lundbeck A/S, and Organon). Dr Per Plenge reported no financial interest or potential conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding: This was an investigator-initiated study where first author served as sponsor. Neuropsykiatrisk Laboratorium paid costs for drug analyses.

None of the below mentioned financial contributors had any part in study design, data collection, analysis or interpretation of data:

Wyeth Denmark contributed with an unrestricted grant. A donation was given from The Tvergaards Foundation and from Johannes M. Klein and wife's memorial Foundation.

ClinicalTrials.gov Identifier: NCT00159146.