Effects on sleep architecture of pindolol, paroxetine and their combination in healthy volunteers.
BACKGROUND
The combination of pindolol with a serotonergic antidepressant has been used to speed up the antidepressant response and to augment in cases of resistant depression. Animal studies have suggested that this increased response occurs because of 5HT(1A) antagonist properties of pindolol, which in combination with a serotonergic antidepressant produces a synergistic increase in 5HT in the synapse.


OBJECTIVE
To test whether the combination of pindolol with a serotonergic antidepressant produces a synergistic increase in synaptic 5HT by examining the effects on measures of sleep, psychomotor performance and ratings of anxiety.


METHODS
Twelve healthy male volunteers took part in randomised crossover study in which they received paroxetine 20 mg/day (or its placebo) for 9 days with a washout period of 5 days between. On day 7 and 9 of each treatment they also received pindolol 2.5 mg (or its placebo) three times a day. Sleep EEG recordings were made on each of the nights on pindolol (or its placebo) and ratings of saccadic eye movement parameters, subjective sleep, anxiety and other adverse events recorded on the following days. Four drug conditions were therefore tested: placebo, pindolol alone, paroxetine alone and paroxetine+pindolol. RESULTS. The combination of paroxetine+pindolol produced an increase in REM suppression and a reduction in SWS compared with other drug combinations. There were no significant effects on the other measures of 5HT function recorded in this study.


CONCLUSIONS
REM suppression by the combination was approximately equal to the sum of REM suppression by each drug individually and thus does not show a synergistic effect. However, there was a significant reduction in SWS produced by only the combination treatment, which may suggest a specific effect of the combination on non-REM sleep mechanisms.
Bell
Caroline
C
Psychopharmacology Unit, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Wilson
Sue
S
Rich
Ann
A
Bailey
Jayne
J
Nutt
David
D
D000328:Adult; D000339:Affect / Q000187:drug effects; D001007:Anxiety / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005133:Eye Movements / Q000187:drug effects; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010869:Pindolol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011674:Pulse; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects
D017374:Paroxetine; D010869:Pindolol; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors