Previously our laboratory has shown that rapid depletion of tryptophan leads to increased panic symptoms in remitted panic patients (Forshall et al. 2000). To test whether tryptophan depletion causes analogous changes in cardiovascular control, fourteen paroxetine-remitted panic patients (mean age 40.6 years; with informed consent; approved by the BRI ethics committee) were treated in a randomised double-blind protocol with either a tryptophan-depletion (TD) diet or a sham tryptophan-containing (NTD) diet on separate days, and they were subjected to either a 2 mg flumazenil (flum) or a vehicle (sal) infusion (randomised double blind) at 4 and 5 h after consumption of the diet. The patients’ blood pressure and heart rate responses to infusion were measured automatically.

Regression models using robust standard error estimators clustered by patient were constructed for systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) changes (▓Dgr│) at 2, 5, 15 and 30 min post-infusion compared with baseline measures 20 min pre-infusion, with the different treatments as the explanatory variables; baseline measures of the independent variable and infusion number were also forced into the models. Using the NTD saline infusion as the basis for comparison, significant differences were found between treatment conditions for ▓Dgr│HR at all time points (i.e. 2, 5, 15 and 30 min: F (3,52) = 4.74*, 3.41*, 7.56** and 6.50**, respectively; P < 0.1, *P < 0.05, **P < 0.01) and ▓Dgr│DBP at 2 and 30 min (F (3,52) = 3.50* and 10.0**).

In the TD flum condition, a trend for an increase in ▓Dgr│SBP (see Fig. 1) and ▓Dgr│HR was observed at almost all time points, but these differences never reached significance. In the TD sal condition, a significant increase was found for the ▓Dgr│HR models at all time points (β = 3.97**, 6.04*, 9.19** and 6.13**, respectively), and marginally significant increases were found in the ▓Dgr│SBP models for all time points (β = 4.82*, 4.07, 8.22 and 8.33, respectively). β values for SBP and DBP were zero or negative at all time points for the NTD flum condition, suggesting no change or a comparative decrease with respect to NTD sal.In conclusion, in comparison with the NTD condition, TD increased the change in SBP, DBP and HR in response to saline infusion; flumazenil showed a tendency to increase these cardiovascular variables in the TD condition but not in the NTD condition. These data are in accordance with the ‘serotonin deficit’ hypothesis of panic.

Figure 1. Regression model for ▓Dgr│SBP at 5 min. Reference treatment (β = 0) is NTD sal.

Forshall, S., Bell, C. & Nutt, D.J. (2000). J. Psychopharmacol. 14 suppl. 3, P14 (A69).