Table 1.

Effect of manipulation of 5-HT synthesis rate on the panic responses

Tryptophan depletion Study	Sample description	Challenge	Study design	Hormones	Main effects
Goddard et al. 1994	8 (4 F) PD patients, mean age 42 ± 7 years	None	Double-blind, crossover	Not measured	No exacerbation in panic or anxiety symptoms
Goddard et al. 1995	11 healthy human subjects	yohimbine	Placebo-controlled	Cortisol	Marked increase in feelings of nervousness following the combination test
Kent et al. 1996	5 (2 F) PD patients, mean age 27.2 ± 7.7 years; 7 (2 F) controls, mean age 28 ± 4 years	5% CO2	Double-blind, crossover	Not measured	Significantly increased ventilation in PD patients, but not in controls. No differences on measures of panic or anxiety
Koszycki et al. 1996	40 healthy male volunteers, mean age 24.6 ± 0.9years	CCK-4	Double-blind, parallel-group	ACTH, cortisol, prolactin	No effects on the panicogenic and cardiovascular responses. Significant rise in ACTH/cortisol and prolactin secretion
Klaassen et al. 1998	15 healthy male volunteers, mean age 29 ± 4 years	35% CO2	Double-blind, crossover	Not measured	Significant increase in both anxiety and neurovegetative panic symptoms
Schruers et al. 2000	24 (15 F) PD patients, mean age 40.0 ± 11.5 years	35% CO2	Double-blind, parallel-group	Not measured	Significant increase in both anxiety and panic symptoms
Miller et al. 2000	20 (10 F) PD patients, mean age 38.4 ± 9.9 years 19 (8 F) healthy controls, mean age 29.1 ± 8.4 years	5% CO2	Double-blind, balanced	Cortisol	Greater anxiogenic response and an increased rate of panic attacks in patients. No effects in controls and no significant changes in cortisol levels.
Hood et al. 2006	14 (9 F) healthy subjects, mean age 34.5 (21–60) years	35% CO2	Double-blind, placebo-controlled, crossover	Cortisol, prolactin	No exacerbation of psychological response and no additive effect on endocrine or cardiovascular responses to challenge
Bell et al. 2002	14 (7 F) recovered PD patients, mean age 40.6 (21–65) years	Flumazenil	Double-blind, placebo-controlled, crossover	Not measured	Significantly higher rate of panic attacks and increased cardiovascular responses following ATD and challenge
Davies et al. 2006	27 (12 F) recovered PD (n = 21) or SAD (n = 6) patients, mean age 39.2 ± 12.0 years	Flumazenil; Autobiographical script	Double-blind, crossover	Not measured	Significant increases in acute stress sensitivity in both cardiovascular and psychological domains on 5-HT depletion
Tõru et al. 2006	18 (12 F) recovered PD patients, mean age 34.5 ± 9.3 years	CCK-4	Double-blind, crossover	Not measured	No significant effects of ATD on psychological or cardiovascular responses
Acute administration of 5-HTP
den Boer and Westenberg, 1990	20 female PD patients, mean age 31.3 ± 7.4 years 20 (F 12) healthy controls, mean age 25.0 ± 2.2 years	None	Single-blind, crossover	Cortisol, β-endorphin, melatonin	Relief effect in patients, but not in controls. Substantial and similar increases in hormones
van Vliet et al. 1996	7 (5 F) PD patients, mean age 34.7 ± 12.6 years 7 (4 F) healthy controls, mean age 21.4 ± 3.6 years	None	Double-blind, placebo-controlled	Cortisol	No provocation of panic or anxiety symptoms, but increase in cortisol levels in both groups after 40 mg 5-HTP infusion
Schruers et al. 2002a, b	24 (11 F) PD patients, mean age 40.0 ± 10.7 years 24 (14 F) healthy controls, mean age 29.8 ± 11.7 years	35% CO2	Double-blind, parallel-group	Cortisol	Significant reduction in both panic and anxiety responses in patients, but not in control group. Significant rise in cortisol levels in both groups following 5-HTP administration
Maron et al. 2004b	32 (18 F) healthy subjects, mean age 21.7 ± 2.8 years	CCK-4	Double-blind, parallel-group	Not measured	Significant reduction in panic attacks and cognitive symptoms in females and decrease in somatic panic symptoms in males