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

Martiny K, Lunde M, Bech P, Plenge P. 

Nord J Psychiatry. 2012 Jun;66(3):147-54. doi: 10.3109/08039488.2012.674553. Epub 2012 Mar 29. PubMed PMID: 22458638.


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.

The object of this study was thus to investigate if pindolol augments the antidepressant response to venlafaxine.

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.

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.

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.

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