Table 1.
Characteristics of included studies.
| Reference | Design | Diagnosis | Sample size N (men) |
Age Mean (SD)a |
ATDb | Challenge | Result Anxiety scores (scale, scores)c | |
|---|---|---|---|---|---|---|---|---|
| Effect of ATD alone compared to control condition or group, unless otherwise specified | Effect of ATD with challenge test compared to control condition of group | |||||||
| Healthy controls | ||||||||
| Smith et al. 1987 (47) | Rand., DB, Betw. SS | HC | 80 (80) | a18–25 | + | - | MAACL: - No sign. effect | |
| Benkelfat et al. 1994 (45) | Rand., DB, within SS | HC |
39 (39) 20 FH + 19 FH- |
FH + 24.1 (2.8) FH- 22.3 (3.4) |
± | - |
POMS anxiety: - Sign. effect (F[1,37] = 13.1, p < 0.001) STAI-S: - No sign. effect (F[1,36] = 3.0, p < 0.095) |
|
| Park et al. 1994 (48) | DB, Within SS | HC | 12 (12) | 29; a21–39 | + | - | VAS anxiety: - No sign. effect | |
| Cleare and Bond 1995 (46) | DB, Betw. SS | HC |
48 (48) 24 HTA 24 LTA |
HTA: 32 (9) LTA: 33 (8) |
+ | Competitive reaction time task |
MRS-anxiety/calmness subscale: - No sign. effect STAI-S:- No sign. effect |
MRS-anxiety/calmness subscale:- No sign. effect STAI-S: - No sign. effect |
| Goddard et al. 1995 (41) | Rand., DB, Within SS | HC | 11 (10) | 27 (2) | ± | Yohimbine |
VAS anxiety:- No sign. effect (F[7,70]=0.91, p = 0.5) VAS nervousness: - No sign. effect (F[7,70]=1.43, p = 0.3) |
VAS anxiety:- No sign. effect of yohimbine-ATD on anxiety compared to yohimbine-alone (F[7,70] = 0.96, p < 0.25) - Sign. effect of yohimbine-ATD on anxiety compared to placebo (F[7,63] = 2.11, p < 0.05) VAS nervousness: - Sign. effect of yohimbine-ATD on anxiety compared to yohimbine-alone (F[7,70] = 3.02, p < 0.005) - Sign. effect of yohimbine-ATD on anxiety compared to placebo (F[7,63] = 4.13, p < 0.0005) |
| Kent et al. 1996 (30) | Rand., Within SS |
HC PD |
HC: 7 (5) PD: 5 (3) |
27.2 (3.96), range 24-34 | + | CO2− 5% | - |
API-IIIR: - No sign. effect 10 point anxiety scale: - No sign. effect 10 point apprehension scale: - No sign. effect Panic attacks: - No sign. effect |
| Koszycki et al. 1996 (31) | Rand., DB, Between SS | HC | 40 (40) | ATD: 23.8 (0.8); Sham-depletion: 25.4 (1.0) | + | CCK-4 | - |
VAS anxiety:- No sign. effect VAS fear:- No sign. effect VAS nervousness: - No sign. effect PSS-IIIR: - No sign. effect Panic attacks: - No sign. effect (χ2 = 0.10, p = 0.75) |
| Klaassen et al. 1998 (32) | Rand., DB, Within SS | HC | 15 (15) | 29 (4) | + | CO2− 35% |
STAI-S: - Sign. effect (Z = −2.02, df = 14, p = 0.04) POMS-tension: - No sign. effect VAS anxiety: - No sign. effect |
VAS anxiety: - No sign. effect PSL-IIIR: - Sign. net increase (post-challenge minus pre-challenge) (Z = −1.96, df = 14, P = 0.05) Panic Attacks: - No sign. effect |
| Miller et al. 2000 (43) | Rand., DB, Within SS |
HC PD |
HC: 19 (11) PD: 20 (10) |
HC: 29.1 (8.4) PD: 38.4 (9.9) |
+ | CO2− 5% |
VAS anxiety: - No sign. effect VAS panic: - No sign. effect POMS: - No sign. effect STAI-S: - No sign. effect Results PD see below |
VAS anxiety: - No sign. effect VAS panic: - No sign. effect POMS: - No sign. effect STAI-S: - No sign. effect API-IIIR: - No sign. effect (F[1,17] = 0.46, p = 0.508) Results PD see below |
| Monteiro-Dos-Santos et al. 2000 (33) | Rand., DB, Betw. SS | HC |
29 (15) ATD: 15 (8) Control (7) |
ATD: 27.9 (1.3) Control: 28.1 (0.9) |
± | SPS | - |
STAI-S: - Sign. effect in females for speech anxiety (F[1,9] = 8.93, p = 0.012), but not in males - VAMS-anxiety: No sign. effect |
| Shansis et al. 2000 (42) | Rand., DB, Within SS | HC | 12 (12) | 23.7: a21–31 | ± | SPS |
POMS: - No sign. effect VAMS: No sign. effect |
VAMS: - - No sign. effect |
| Colasanti et al. 2011 (35) | Rand., DB, Within SS | HC | 18 (10) | 25 (5.5) | + | CO2− 35% |
VAAS: - No sign. effect PSL-IV: - No sign. effect POMS: - No sign. effect |
VAAS: - Sign. effect (F = 5.79, p < 0.05, df’s not reported) PSL-IV: - No sign. effect |
| Robinson et al. 2012 (53) | Rand., DB, Within SS | HC | 20 (13) | 25.1 (5.6) | + | Startle Paradigm | STAI-S: - No sign. effect (p > 0.1) |
STAI-S: - No sign. effect (p > 0.1) Retrospective anxiety: - No sign. effect (p > 0.1) |
| Remitted patients | ||||||||
| Bell et al. 2002 (38) | Rand., DB, Within SS | PD remitted with SSRI >12 wks | 14 (7) | 40.6; a 21–65 | + | Flumazenil |
STAI-S: - No sign. effect PSI: - Sign. effect at 240 min (t = 2.946;df = 14; p < 0.05) VAS anxiety: - No sign. effect Panic attacks: - Sign. effect with 10/14 or with tighter PSI definition 7/14 panic attacks in ATD condition compared to 1/14 in control condition (p = 0.016) |
STAI-S: - No sign. effect PSI: - No sign. effect VAS anxiety: - No sign. effect |
| Argyropoulos et al. 2004 (39) | Rand., DB, Within SS | SAD remitted on SSRI | 14 (9) | 39.9 (11.2), range 21–58 | ± | ABS |
STAI-S: - Sign. effect (F[1,12] = 9.369, p = 0.01) VAS anxiety: - No sign. effect (p = 0.20) |
STAI-S: - Sign. effect for autobiographical script (z = −2.28, p = 0.02) and neutral script (z = −2.2, p = 0.03), but not for verbal task (z = 1.49, p = 0.14) VAS anxiety: - Sign. effect for autobiographical script (z = −2.26, p = 0.02), but not for neutral script (z = −0.31, p = 0.75) or verbal task (z = −0.34, p = 0.73) |
| Davies et al. 2006 (36) | Rand., DB, Within SS |
PD with - SSRI - CBT SAD with SSRI |
27 (15) 14 7 6 |
39.2 (12.0) | + |
Flumazenil ABS |
STAI-S: - No sign. effect (p = 0.385) PSI - No sign. effect (p = 0.052) |
STAI-S: - Sign. effect (p = 0.001) PSI: - Sign. effect (p = 0.013) |
| Tõru et al. 2006 (28) | Rand., DB, Within SS |
PD remitted on SSRI >2 wks |
18 (6) | 34.5 (9.3) | + | CCK-4 |
VAS anxiety: - No sign. effect PSS-IV: - No sign. effect |
VAS anxiety: - No sign. effect (U = 161.0, p = 0.99) PSS-IV: - No sign. effect (p = 0.70) Panic attacks: - No sign. effect (χ2 = 0.13, df = 1, p = 0.72) |
| Hood et al. 2010 (37) | Rand., DB, Within SS | GAD remitted on SSRI | 11 (5) | 37.5 (12.2) | + | Chronic CO2−7,5% |
STAI-S: - No sign. effect VAS anxiety: - No sign. effect POMS: - - No sign. effect |
|
| Bell et al. 2011 (44) | Rand., DB, Within SS | PD remitted on CBT | 9 (5) | 33.2, range 20–43 | + | Flumazenil |
STAI-S: - No sign. effect PSI: - No sign. effect VAS anxiety: - No sign. effect |
STAI-S: - Sign. effect (F[3,24] = 3.1, p = 0.04) PSI: - No sign. effect (F[3, 240] = 1.5, p = 0.240) VAS anxiety: - No sign. effect (F[1,24] = 3.9, p = 0.08) Panic attacks: - No sign. effect (p = 0.625) |
| Patients | ||||||||
| Goddard et al. 1994 (40) | Rand., DB, Within SS | PD (unmedicated) | 8 (4) | 42 (7) | + | - |
VAS anxiety: - No sign. effect Panic attacks: - No sign. effect |
|
| Kent et al. 1996 (30) | Rand., Within SS |
HC PD |
HC: 7 (5) PD: 5 (3) |
27.2 (3.96), range 24–34 | + | CO2− 5% | Results for patients were the same as for healthy volunteers (see above) | |
| Miller et al. 2000 (43) | Rand., DB, Within SS |
HC PD |
HC: 19 (11) PD: 20 (10) |
HC: 29.1 (8.4) PD: 38.4 (9.9) |
+ | CO2− 5% |
VAS anxiety: - No sign. effect VAS panic: - No sign. effect up to 240 min. - Sign. effect between 240–270 min (F[1,37] = 4.37, p = 0.043) POMS: - No sign. effect STAI-S:- No sign. effect |
VAS anxiety: - No sign. effect (F[2,34] = 3.07, p = 0.060) VAS panic:- Sign. effect (F[2,34] = 6.14, p = 0.005) POMS:- No sign. effect STAI-S: - No sign. effect API:- Sign. effect (F[1,34] = 23.06, p < 0.001) |
| Schruers et al. 2000 (34) | Rand., BD, Betw. SS | PD |
24 (9) Depletion: 12 (5) Control 12 (4) |
Depletion: 43 (12) Control (37 (11) |
+ | CO2− 35% |
PSL-IV: - No sign. effect VAAS: - No sign. effect |
PSL-IV: - Sign. effect (p < 0.02) VAAS: - Sign. effect (p < 0.05) Panic attacks:- Sign. effect (p < 0.01) |
ABS autobiographic script, API Acute Panic Inventory, ATD acute tryptophan depletion, Betw. SS between-subjects design, CBT cognitive behaviour therapy, CCK-4 tetrapeptide central cholecystokinin receptor agonist, CO2 carbon dioxide, DB double-blind, FH multigenerational family history of affective illness, GAD generalised anxiety disorder, HC healthy controls, HTA high trait aggression, LTA low trait aggression, MAACL Multiple Affect Adjective Checklist, MRS mood rating scale, PD panic disorder, POMS Profile of Mood States, PSI panic symptom inventory, PSL panic symptom list, PSS panic symptom scale, Rand. randomised, SAD social anxiety disorder, sign. significant, SPS simulated public speaking, STAI-S state part of State Trade Anxiety Inventory, SSRI selective serotonin reuptake inhibitor, VAAS visual analogue anxiety scale, VAMS Bond and Lader visual analogue mood scale, VAS visual analogue rating scale, Within SS Within subjects design.
aIf the Mean or SD was not reported, the range is noted.
bATD + : good depletion, ±: unclear level of depletion was adequate.
cStatistics only reported if described in original article.