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. 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.