Tryptophan depletion does not modify response to CCK-4 challenge in patients with panic disorder after treatment with citalopram.
BACKGROUND
Data by [Bell et al. J Psychopharmacol (2002) 16:5-14] suggest that a decrease in 5-HT neurotransmission predisposes to panic attacks and that the antipanic effect of SSRIs depends upon the availability of 5-HT in the brain.


OBJECTIVE
Our aim was to assess the effect of acute tryptophan depletion (TD) on cholecystokinin-tetrapeptide (CCK-4)- induced symptoms in patients with panic disorder (PD) who had responded to a 10-week treatment with a selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram.


METHODS
A total of 18 patients (6 males and 12 females, mean age 34.5 years) received a tryptophan-free amino acid drink and a control drink, each followed by a CCK-4 challenge (25 microg), 1 week apart in a double-blind crossover design.


RESULTS
The results showed no significant differences in response to the CCK-4 challenge between the TD and the control conditions. Panic rate after the CCK-4 challenge was 27.8% after depletion and 33.3% after control drink (chi2=0.13, p=0.72). No significant effects of TD were observed in panic intensity scores, subjective anxiety, or cardiovascular indices.


CONCLUSIONS
This study demonstrates that an acute lowering of brain 5-HT availability with TD does not affect response to a CCK-4 challenge in PD patients successfully treated with citalopram. Thus, the reduction of CCK-4 sensitivity following SSRI-treatment in patients with PD may be related to mechanisms other than 5-HT availability in the brain, possibly to a reduction in brain cholecystokinin receptor sensitivity.
Department of Psychiatry, University of Tartu, Tartu, Estonia. Innar.Toru@kliinikum.ee
Innar
I
Tõru
Jakov
J
Shlik
Eduard
E
Maron
Veiko
V
Vasar
David J
DJ
Nutt
D000328:Adult; D015283:Citalopram / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000139:chemically induced / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013758:Tetragastrin / Q000009:adverse effects*; D014364:Tryptophan / Q000172:deficiency*
D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D013758:Tetragastrin; D014364:Tryptophan