Pindolol augmentation of selective serotonin reuptake inhibitors: PET evidence that the dose used in clinical trials is too low

Am J Psychiatry. 2001 Dec;158(12):2080-2. doi: 10.1176/appi.ajp.158.12.2080.

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.

Method: 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.

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pindolol / administration & dosage*
  • Pindolol / adverse effects
  • Pindolol / pharmacokinetics
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Receptors, Serotonin, 5-HT1
  • Selective Serotonin Reuptake Inhibitors / administration & dosage*
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / pharmacokinetics
  • Tomography, Emission-Computed*
  • Treatment Outcome

Substances

  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Uptake Inhibitors
  • Pindolol