Pindolol augmentation of selective serotonin reuptake inhibitors: accounting for the variability of results of placebo-controlled double-blind studies in patients with major depression.

Co-administration of pindolol with SSRIs in patients with depression has been suggested as a way to both hasten and augment antidepressant response. Clinical trials have examined the efficacy of this treatment regime and conflicting results have been reported. The present review briefly presents the results of placebo-controlled double-blind trials of pindolol augmentation of SSRIs in patients with major depression, and focuses on factors that may account for the variability of findings. Additionally, a profile of the subset of patients who may most benefit from pindolol augmentation is outlined. Methodological factors such as qualitative differences in definitions of antidepressant response, the timing of pindolol administration and heterogeneous clinical characteristics of patient samples may contribute to the variability in the results of clinical trials to date. Similarly, individual differences in neuropathology, neurophysiology and genotype may also account for some of the inconsistencies in the findings. Finally, the results of recent neuroimaging studies suggest that the 2.5 mg t.i.d. dose of pindolol that has been used in all but one of these investigations may be suboptimal for achieving reliable and significant occupancy of 5-HT1A autoreceptors and may explain the contradictory nature of the results of investigations of pindolol augmentation.