Abstract
Preclinical studies suggest that augmentation of selective serotonin (5-HT) reuptake
inhibitors by the 5-HT1A receptor agent pindolol might reduce the delay between initiation of treatment and
antidepressant response, an effect largely mediated by blockade of 5-HT1A autoreceptors in the dorsal raphe nuclei. Although some controlled clinical trials
suggest that pindolol might reduce latency to selective serotonin reuptake inhibitor
response in acute depressive episodes, the effect is moderate and highly variable.
Recent positron emission tomography studies investigating the occupancy of 5-HT1A receptors in humans by pindolol have shown that at the dose used most often in clinical
trials the occupancy is low and variable, which might explain the inconsistent clinical
results. Positron emission tomography studies also suggest that pindolol might be
more potent at blocking 5-HT1A autoreceptors than at blocking postsynaptic receptors, a property that may be useful
in this pharmacologic strategy. Thus, the positron emission tomography data support
the potential of pindolol to augment the antidepressant response of selective serotonin
reuptake inhibitors, but also imply that this potential has not been fully evaluated.
Here we review the clinical trials, the positron emission tomography studies, and
the possible mechanisms of pindolol augmentation. It is also suggested that positron
emission tomography may be used to define therapeutic dosing early on in the process
of clinical evaluation of new treatment strategies.
Keywords
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Article info
Publication history
Accepted:
July 19,
2000
Received in revised form:
July 11,
2000
Received:
May 2,
2000
Identification
Copyright
© 2000 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
