The effects of single dose anxiolytic medication on the CO2 models of anxiety:
differentiation of subjective and objective measures.
Author(s): Papadopoulos A, Rich A, Nutt DJ, Bailey JE.
Affiliation(s): Psychopharmacology Unit, University of Bristol, Bristol, UK.
Publication date & source: 2010, J Psychopharmacol. , 24(5):649-56
This was a double blind, placebo-controlled, 4-way cross-over study in 12 healthy
volunteer subjects of the acute effects of three drugs each of which are used in
the clinic to treat some forms of anxiety: propranolol 40 mg, hydroxyzine 25 mg,
flupentixol 0.5 mg and placebo. Each test session consisted of inhalation of air
for 20 min, 10-min rest, inhalation of CO2 7.5% for 20 min, 10-min rest, followed
by a single vital capacity inhalation of 35% CO2. The CO2 7.5% was administered
at peak drug effect. Subjective effects were measured using Visual Analogue
Scales (VAS), the Panic Symptom Inventory and the Generalised Anxiety Disorder
Assessment inventory. Twelve subjects participated (eight men), with a mean age
of 25.9 years. The expected subjective effects of CO2 were seen and these were
significantly different from effects of peak air. However, there were no
statistically significant differences between the drugs or between drugs and
placebo, indeed there was a trend for some VAS anxiety scores to be higher than
placebo in the drug groups. There were some significant differences in
cardiovascular responses to CO2, with propranolol significantly decreasing heart
rate and flupentixol increasing blood pressure when compared with placebo. The
lack of subjective anxiolytic actions of the three drugs contrasts with our
previous findings with acute benzodiazepines and chronic selective serotonin
reuptake inhibitor administration. It may be that prolonged treatment with these
agents would be required to show anxiolytic effects, although it may also be that
their efficacy is insufficient to be demonstrated in this model. The lack of
anxiolytic actions of propranolol, despite a significant reduction in heart rate,
is a further support for a central action of CO2 to produce anxiety.