The effects of single dose anxiolytic medication on the CO2 models of anxiety: differentiation of subjective and objective measures.
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.
Papadopoulos
A
A
Psychopharmacology Unit, University of Bristol, Bristol, UK.
Rich
A
A
Nutt
D J
DJ
Bailey
J E
JE
D000280:Administration, Inhalation; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001143:Arousal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000502:physiology / Q000633:toxicity*; D002319:Cardiovascular System / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005475:Flupenthixol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006919:Hydroxyzine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D014797:Vital Capacity; D055815:Young Adult
D014151:Anti-Anxiety Agents; D002245:Carbon Dioxide; D006919:Hydroxyzine; D011433:Propranolol; D005475:Flupenthixol