Pindolol augmentation of selective serotonin reuptake inhibitors: PET evidence that the dose used in clinical trials is too low.
OBJECTIVE
Positron emission tomography (PET) was used to examine whether the dose of pindolol used to augment antidepressant medication achieves a significant occupancy of the serotonin type 1A (5-HT(1A)) autoreceptor in depressed patients receiving medication.


METHODS
The authors examined eight depressed patients on one of two regimes of pindolol (2.5 mg t.i.d. and 5.0 mg t.i.d.) with PET and [11C]WAY-100635.


RESULTS
The 5-mg t.i.d. regime achieved a modest (19%) but significant occupancy of the 5-HT(1A) autoreceptor, while the regime used in the vast majority of clinical trials (2.5 mg t.i.d.) did not achieve a significant occupancy.


CONCLUSIONS
The dose of pindolol used in clinical trials is suboptimal and may explain the inconsistent results. Therefore, a thorough test of pindolol's efficacy will necessitate doses higher than those used in present clinical trials.
Rabiner
E A
EA
MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK. eugenii.rabiner@ic.ac.uk
Bhagwagar
Z
Z
Gunn
R N
RN
Sargent
P A
PA
Bench
C J
CJ
Cowen
P J
PJ
Grasby
P M
PM
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
D010869:Pindolol; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017367:Selective Serotonin Reuptake Inhibitors