Pindolol augmentation of antidepressant treatment: recent contributions from brain imaging studies.
Preclinical studies suggest that augmentation of selective serotonin (5-HT) reuptake inhibitors by the 5-HT(1A) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response, an effect largely mediated by blockade of 5-HT(1A) 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-HT(1A) 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-HT(1A) 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.
Martinez
D
D
Department of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York 10032, USA.
Broft
A
A
Laruelle
M
M
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004357:Drug Synergism; D005473:Fluoxetine / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D017374:Paroxetine / Q000378:metabolism* / Q000627:therapeutic use*; D010869:Pindolol / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D014055:Tomography, Emission-Computed
D005473:Fluoxetine; D017374:Paroxetine; D010869:Pindolol; D017367:Selective Serotonin Reuptake Inhibitors