title: Pindolol augmentation of selective serotonin reuptake inhibitors: PET evidence that the dose used in clinical trials is too low.
abstract: 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.
authors.affiliation: MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK. eugenii.rabiner@ic.ac.uk
authors.forename: E A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: Z
authors.initials: Z
authors.lastname: Bhagwagar
authors.forename: R N
authors.initials: RN
authors.lastname: Gunn
authors.forename: P A
authors.initials: PA
authors.lastname: Sargent
authors.forename: C J
authors.initials: CJ
authors.lastname: Bench
authors.forename: P J
authors.initials: PJ
authors.lastname: Cowen
authors.forename: P M
authors.initials: PM
authors.lastname: Grasby
mesh_terms: 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
chemical_list: D010869:Pindolol; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017367:Selective Serotonin Reuptake Inhibitors