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Forman-Hoffman V, Middleton JC, Feltner C, et al. Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 May. (Comparative Effectiveness Review, No. 207.)
Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update [Internet].
Show detailsKey Question 1
Table I-1Cognitive processing therapy compared with inactive controls (waitlist or usual care)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline to end of treatment in CAPS | ||||||
| 5; 399 | Medium; RCTs | Consistent | Direct | Imprecise | SMD -1.35 (95% CI, -1.77 to -0.94) | Moderate |
| Loss of Diagnosis | ||||||
| 4; 299 | Medium; RCTs | Consistent | Direct | Imprecise | RD 0.44 (95% CI, 0.26 to 0.62) | Moderate |
| Prevention/reduction of comorbid depression: mean change from baseline to end of treatment in BDI | ||||||
| 5; 399 | Medium; RCTs | Consistent | Direct | Precise | SMD -1.09 (95% CI, -1.52 to -0.65) | Moderate |
| Prevention/reduction of comorbid anxiety: mean change from baseline to end of treatment in STAI | ||||||
| 2; 119 | Medium; RCTs | Inconsistent | Direct | Imprecise | One trial significantly favored CPT, the other found no differences | Insufficient |
| Quality of Life | ||||||
| 2; 159 | Medium; RCT | Inconsistent | Direct | Imprecise | One trial significantly favored CPT, the other found no differences in physical quality of life measures | Insufficient |
CAPS = Clinician Assessment PTSD Scale; CI = confidence interval; CPT = cognitive processing therapy; CR = cognitive restructuring; NA = not applicable; NNT = number needed to treat; RA = repeated assessments (a type of waitlist control group); RCT = randomized controlled trial; RD = risk difference; STAI = State-Trait Anxiety Inventory; UC = usual care; WL = waitlist
Table I-2Cognitive therapy compared with inactive controls (waitlist or usual care)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline to end of treatment | ||||||
| 4; 236 | Medium; RCTs | Consistent | Direct | Imprecise | SMD range −2.0 to −0.3, p<0.05 for 4 of 4 trials. | Moderate |
| Loss of Diagnosis | ||||||
| 4; 283 | Medium; RCTs | Consistent | Direct | Imprecise | RD 0.55 (95% CI, 0.28 to 0.82). | Moderate |
| Prevention/reduction of comorbid depression: mean change from baseline to end of treatment on BDI | ||||||
| 4; 283 | Medium; RCTs | Consistent | Direct | Imprecise | WMD range −11.1 to −8.3 N=283, p<0.05 for 4 of 4 trials. | Moderate |
| Prevention/reduction of comorbid anxiety: mean change from baseline to end of treatment in BAI | ||||||
| 4; 284 | Medium; RCTs | Consistent | Direct | Imprecise | WMD range −5.6 to −18.7, p<0.05 for 3 of 4 trials | Moderate |
| Quality of Life | ||||||
| 2; 199 | Medium; RCT | Inconsistent | Direct | Imprecise | One trial significantly favored CT, the other found no differences in mental quality of life measures | Insufficient |
| Disability/functional impairment; mean change in SDS from baseline to posttreatment | ||||||
| 3; 176 | Medium; RCTs | Consistent | Direct | Precise | WMD range −11.3 to −2.2, p<0.05 for 3 of 3 trials | Moderate |
- a
Included trials compared CT with waitlist (Ehlers 2003 and Ehlers 2005), a self-help booklet (Ehlers 2003), and usual care (Muesser 2008).
- b
Data were based on meta-analysis of CAPS total for Muesser 2008 and CAPS-intensity for the Ehlers 2003 and 2005 studies.
- c
Direction of effects were consistent; magnitude of effects ranged from very large to small
BAI = Beck Anxiety Inventory; CI = confidence interval; NA = not applicable; NNT = number needed to treat; RCT = randomized controlled trial; RD = risk difference; WL = waitlist.
Table I-3Metacognitive therapy compared with inactive controls (waitlist or usual care)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline to end of treatment | ||||||
| 1; 21 | Medium; RCTs | NA, single study | Direct | Imprecise | WMD −27.7 | Insufficient |
| Prevention/reduction of comorbid depression: mean change from baseline to end of treatment in BDI | ||||||
| 1; 21 | Medium; RCTs | NA, single study | Direct | Imprecise | Findings favor MCT, p<0.05 | Insufficient |
| Prevention/reduction of comorbid anxiety: mean change from baseline to end of treatment in BAI | ||||||
| 1; 21 | Medium; RCTs | NA, single study | Direct | Imprecise | Findings favor MCT, p<0.05 | Insufficient |
BAI = Beck Anxiety Inventory; CI = confidence interval; NA = not applicable; NNT = number needed to treat; RCT = randomized controlled trial; RD = risk difference; WL = waitlist.
Table I-4Stress inoculation training compared with waitlist
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: PSS-I | ||||||
| 1; 41 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −10.5, p<0.05 | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 41 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.42, p<0.05 | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 41 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −8.5, p<0.05 | Insufficient |
| Prevention/reduction of comorbid anxiety: STAI | ||||||
| 1; 41 | Medium; RCT | NA, single study | Direct | Imprecise | WMD, −11.4, p=ns | Insufficient |
BDI =; CI = confidence interval; NA = not applicable; PSS-I = Posttraumatic Stress Disorder Symptom Scale-Interview; RCT = randomized controlled trial
Table I-5Relaxation compared with treatment as usual
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction | ||||||
| 1; 25 | Medium; RCT | NA, single study | Direct | Imprecise | p=ns for 3 different measures | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 25 | Medium; RCT | NA, single study | Direct | Imprecise | Favor relaxation but significance not reported | Insufficient |
| Prevention/reduction of comorbid anxiety: STAI | ||||||
| 1; 25 | Medium; RCT | NA, single study | Direct | Imprecise | Favor relaxation but p=ns | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-6Relaxation compared with cognitive restructuring
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: percentage of patients with at least 50% decrease in PSS symptoms at posttreatment | ||||||
| 1; 34a | Medium; RCT | NA, single study | Direct | Imprecise | RD, 0.17 favoring CR, p=ns | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 34a | Medium; RCT | NA, single study | Direct | Imprecise | RD, 0.10 favoring CR, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: BDI, mean change scores (im provement) | ||||||
| 1; 34a | Medium; RCT | NA, single study | Direct | Imprecise | WMD −5.0 favoring CR, p=ns | Insufficient |
| Prevention/reduction of comorbid anxiety | ||||||
- a
Total trial N was 81. Subjects were randomized to PE (23), CR (13), CBT- Mb (CR+PE) (24), or relaxation (21).122
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-7Mindfulness Based Stress Reduction compared with treatment as usual
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: PCL | ||||||
| 1; 50 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −3.0, p<0.05 | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 50 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −2.8, p<0.05 | Insufficient |
CI = confidence interval; NA = not applicable; PSS-I = Posttraumatic Stress Disorder Symptom Scale-Interview; RCT = randomized controlled trial
Table I-8Neurofeedback training compared with waitlist
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 52 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −20.3, p<0.05; also significant decreases in DTS scores | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 52 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.40, p<0.05 | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 41 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −8.5, p<0.05 | Insufficient |
| Prevention/reduction of comorbid anxiety: STAI | ||||||
| 1; 41 | Medium; RCT | NA, single study | Direct | Imprecise | WMD, −11.4, p=ns | Insufficient |
CI = confidence interval; NA = not applicable; PSS-I = Posttraumatic Stress Disorder Symptom Scale-Interview; RCT = randomized controlled trial
Table I-9Exposure-based therapies compared with inactive controls (waitlist or usual care)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS and all PTSD symptom measures | ||||||
| 13; 885 (all); 8; 689 (CAPS) | Medium; RCTs | Consistent | Direct | Precise | SMD -1.23 (95% CI, -1.50 to -0.97) SMD(CAPS) -1.12 (95% CI, -1.42 to -0.82)) | High |
| Loss of Diagnosis | ||||||
| 6; 409 | Medium; RCTs | Consistent | Direct | Precise | RD 0.56 (95% CI, 0.35 to 0.78) | High |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 10; 715 | Medium; RCTs | Consistent | Direct | Precise | SMD -0.76 (95% CI, -0.91 to 0.60) | High |
| Prevention/reduction of comorbid anxiety | ||||||
| 3; 286 | N/A | Consistent | Direct | Imprecise | All favored CBT-exposure, p<0.05 for 2 of 3 | Low |
| Disability/functional impairment | ||||||
| 2; 221a | Medium; RCTs | Inconsistent | Direct | Imprecise | Small trial (N=31) favored CBT-exposure, p<0.05 but other larger trial found no differences, p=ns | Insufficient |
- a
One trial did not provide sample sizes of each group, so this total includes the PE+CR group which was not included in this analysis.
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-10Exposure-based therapy compared with cognitive restructuring
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 38 | Medium; RCT | NA, single study | Direct | Imprecise | p<0.05 | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 38 | Medium; RCT | NA, single study | Direct | Imprecise | p<0.05 | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 38 | Medium; RCT | NA, single study | Direct | Imprecise | p<0.05 | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-11Exposure-based therapy compared with cognitive therapy
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1;62 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −4.0, p<0.05 | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 62 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.16, p<0.05 | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 62 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −1.9, p<0.05 | Insufficient |
| Prevention/reduction of comorbid anxiety | ||||||
| 1; 62 | Medium; RCT | NA, single study | Direct | Imprecise | P<0.05 | Insufficient |
| Return to work or return to active duty: % of subjects actively working at 6 month follow up | ||||||
| 1; 62 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.07, p=ns | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-12Exposure-based therapy compared with cognitive processing therapy
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 124 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −4.0, p=ns | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 124 | Medium; RCT | NA, single study | Direct | Imprecise | WMD 0, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 124 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −2.9, p=ns | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-13Exposure-based therapy compared with metacognitive therapy
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: PDS | ||||||
| 1; 22 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −10.5, p<0.05 | Insufficient |
| Loss of Diagnosis | ||||||
| 1;22 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.30, unknown statistical significance | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1;22 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −7.6, p<0.05 | Insufficient |
| Prevention/reduction of comorbid anxiety: BAI | ||||||
| 1;22 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −4.7, p<0.05 | Insufficient |
BAI = Beck Anxiety Inventory; BDI = Beck Depression Inventory; CI = confidence interval; NA = not applicable; RCT = randomized controlled trial.
Table I-14Exposure-based therapy compared with stress inoculation training
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 51 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −1.8, p=ns | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 51 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.18, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 51 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −0.2, p=ns | Insufficient |
NA = not applicable
Table I-15Exposure-based therapy compared with relaxation
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 3; 155 | Medium; RCTs | Consistent | Direct | Imprecise | SMD -0.45 (-0.78 to -0.13), 3 trials, N=155 | Moderate |
| Loss of Diagnosis | ||||||
| 2; 85 | Medium; RCTs | Consistent | Direct | Imprecise | RD range 0,20 to 0.47, both trials favored CBT-exposure, p<0.05 in 2 of 2 trials | Moderate |
| Prevention/reduction of comorbid depression: BDI or HAM-D | ||||||
| 3; 155 | Medium; RCTs | Consistent | Direct | Imprecise | SMD -0.39 (-0.71 to -0.07), 3 trials, N=155; | Moderate |
NA = not applicable
Table I-16Exposure-based therapy compared with EMDR
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 3; 199 | 2 Medium, 1 Low; RCTs | Consistent | Direct | Imprecise | P=ns in 3 of 3 trials | Low for no difference |
| Symptom Remission | ||||||
| 0; 0 | NA | NA | NA | NA | NA | Insufficient |
| Loss of Diagnosis | ||||||
| 3; 199 | 2 Medium, 1 Low; RCTs | Inconsistent | Direct | Imprecise | No significant difference between groups, 2 of 3 favored PE and 1 of 3 favored EMDR | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 2; 91 | Medium; RCTs | Consistent | Direct | Imprecise | P=ns | Insufficient |
CI = confidence interval; NA = not applicable; PE = prolonged exposure; RCT = randomized controlled trial
Table I-17Exposure-based therapy compared with IPT
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 78 | Medium; RCT | NA, single study | Direct | Imprecise | p=ns | Insufficient |
| Symptom Remission | ||||||
| 1;78 | NA | NA, single study | NA | NA | RD 0.03, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: HAM-D | ||||||
| 1;78 | Medium; RCT | NA, single study | Direct | Imprecise | p=ns | Insufficient |
| Quality of Life | ||||||
| 1; 78 | Medium, RCT | NA, single study | Direct | Imprecise | No significant difference between PE and IPT (−17.9 vs. −11.3, p=0.061) | Insufficient |
CI = confidence interval; NA = not applicable; PE = prolonged exposure; RCT = randomized controlled trial
Table I-18Exposure-based therapy compared with exposure therapy + cognitive restructuring
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS or PSS-I | ||||||
| 4; 299 | Medium; RCTs | Inconsistent | Direct | Imprecise | Two studies favored exposure + CR, one study favored CR; p=ns for 4 of 4 trials | Insufficient |
| Loss of Diagnosis | ||||||
| 3; 146 | Medium; RCTs | Imprecise | Direct | Imprecise | P=ns for 3 of 3 studies, one favored PE and two favored PE+CR | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 4; 299 | Medium; RCTs | Consistent | Direct | Imprecise | P=ns in 4 of 4 studies | Low for no benefit |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-19CBT-mixed interventions compared with inactive controls (waitlist, usual care)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistencya | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline to end of treatment for CAPS, all PTSD symptom measures | ||||||
| 11; 709 (CAPS) 21; 1349 (all PTSD symptom measures) | Medium; RCTs | Consistent | Direct | Precise | SMD -1.01 (95% CI, -1.28 to -0.74) SMD (CAPS) -1.24 (95% CI, -1.67 to -0.81) | High |
| Remission (PCL) | ||||||
| 1; 44 | Medium; RCTs | NA, single study | Direct | Imprecise | 0.40 | Insufficient |
| Loss of Diagnosis | ||||||
| 9; 474 | Medium; RCTs | Consistent | Direct | Precise | RD 0.29 (0.17, 0.40) | High |
| Prevention/reduction of comorbid depression: mean change from baseline in BDI | ||||||
| 15; 929 | Medium; RCTs | Consistent | Direct | Precise | SMD -0.87 (95% CI, -1.14 to -0.61) | High |
| Prevention/reduction of comorbid anxiety: mean change from baseline in STAI | ||||||
| 5; 257 | Medium; RCTs | Consistent | Direct | Imprecise | WMD, −10.4 (−18.0 to −2.8); 5 trials, N=257; I squared=82.9 | Moderate |
| Quality of Life | ||||||
| 5; 416 | Medium; RCTs | Inconsistent | Direct | Imprecise | Mixed results (3 of 5 no difference p=ns; 2 of 5 favored CBT-M p<0.05) | Insufficienta |
| Disability/functional impairment | ||||||
| 6; 350 | Medium; RCTs | Consistent | Direct | Imprecise | All trials favored CBT-M, 4 of 6 met statistical significance. | Lowb |
- a
The use of four difference quality of life measures149 across the five trials, (one of which included only subscale data, precluded the use of meta-analysis to pool findings). We downgraded the SOE grade for these inconsistencies further due to heterogeneity in measures.
- b
We did not use meta-analysis to pool findings because of the diversity of measures used to different aspects of disability and functional impairment. We downgraded the SOE grades for these inconsistencies further due to heterogeneity in measures.
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-20CBT-mixed interventions compared with relaxation: Head-to-head trials
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction by CAPS | ||||||
| 2; 85 | Medium; RCTs | Consistent | Direct | Imprecise | WMD range −24.0 to −21.2, p<0.05 in 2 of 2 trials | Low |
| Disability/functional impairment by GHQ Global Improvement | ||||||
| 1; 45 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.15, p=NS | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-21EMDR compared with inactive controls (waitlist, usual care)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction | ||||||
| 8; 449 | Medium; RCTs | Consistent | Direct | Imprecise | SMD -1.08 (95% CI, -1.82 to -0.35) | Moderate |
| Loss of Diagnosis | ||||||
| 7; 427 | Medium; RCTs | Consistent | Direct | Imprecise | RD 0.43 (0.25 to 0.61) | Moderate |
| Prevention/reduction of comorbid depression | ||||||
| 7; 347 | Medium; RCTs | Consistent | Direct | Imprecise | SMD -0.91 (95% CI, -1.58 to 0.24) | Moderate |
| Prevention/reduction of comorbid anxiety: mean change from baseline in STAI | ||||||
| 4; 167 | Medium; RCTs | Inconsistent | Direct | Imprecise | No significant difference in 3 of 4 trials. | Insufficient |
CI = confidence interval; EMDR = eye movement desensitization and reprocessing; NA = not applicable; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial; RD = risk difference; SMD = Standardized mean difference; STAI = State Trait Anxiety Inventory; WMD = weighted mean difference
Table I-22EMDR compared with relaxation
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction | ||||||
| 2; 64 | Medium; RCTs | Inconsistent | Direct | Imprecise | Inconsistent findings across studies | Insufficient |
| Loss of Diagnosis at 3 month post-treatment followup | ||||||
| 2; 64 | Medium; RCTs | Inconsistent | Direct | Imprecise | Inconsistent findings across studies | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 2; 64 | Medium; RCTs | Inconsistent | Direct | Imprecise | Inconsistent findings across studies | Insufficient |
| Prevention/reduction of comorbid anxiety: STAI | ||||||
| 1; 23 | Medium; RCT | NA, single study | Direct | Imprecise | Cohen’s d=1.15 (favoring EMDR), p<0.01 | Insufficient |
- a
Two SMDs reported here because two meta-analyses were run because one of the two trials reported two measures of PTSD symptoms.46 The first SMD is from our meta-analysis using the Mississippi Scale for Combat Related PTSD from the study reporting two measures; the second is using the IES from that trial. The other trial reported the CAPS.133
BDI = Beck Depression Inventory; CAPS = Clinician-Administered Post Traumatic Stress Disorder Scale; CI = confidence interval; EMDR = eye movement desensitization and reprocessing; NA = not applicable; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Table I-23Seeking safety compared with inactive comparators
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS frequency and intensity, reduction from baseline to post-treatment | ||||||
| 3; 232 | Medium; RCT | Consistent | Direct | Imprecise | SMD of individual trials ranged from -0.22 to 0.04 Two of three trials favored treatment (no study p<0.05) | Low for no difference |
| Prevention/reduction of comorbid substance use | ||||||
| 2; 163 | Medium; RCT | Inconsistent | Direct | Imprecise | Mixed findings, p<0.05 for drug use but not alcohol use in 1 of 2 trials | Insufficient |
CAPS = Clinician-Administered Post Traumatic Stress Disorder Scale; BDI = Beck Depression Inventory; CI = confidence interval; IES = Impact of Events Scale; NA = not applicable; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Table I-24Imagery rehearsal therapy (IRT) compared with waitlist (1 trial)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS mean change from baseline | ||||||
| 1; 168 | Medium; RCT | NA, Single study | Direct | Imprecise | WMD −21.0, p<0.05 | Low |
| Prevention/reduction of comorbid depression: HAMD | ||||||
| 1; 168 | Medium; RCT | NA, Single study | Direct | Imprecise | p=ns | Insufficient |
| Prevention/reduction of comorbid anxiety: HAMA | ||||||
| 1; 168 | Medium; RCT | NA, Single study | Direct | Imprecise | p=0.04 because symptoms increased in inactive comparator group at followup | Insufficient |
CAPS = Clinician-Administered Post Traumatic Stress Disorder Scale; CI = confidence interval; HAM-D = Hamilton Depression Scale; HAM-A = Hamilton Anxiety Scale; IRT = imagery rehearsal therapy; NA = not applicable; NR = Not Reported; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial; SF-36 = 36-Item Short-Form Health Survey; WL = waitlist
Table I-25Narrative exposure therapy (NET) compared with an inactive control (waitlist or MA)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline to post-treatment in PDS and CAPS | ||||||
| 3; 232 | Medium; RCTs | Consistent | Direct | Imprecise | SMD ranged from -1.95 to -0.79 across 3 individual studies (3 of 3 studies p<0.05) | Moderate |
| Loss of Diagnosis | ||||||
| 2; 198 | Medium; RCTs | Consistent | Direct | Imprecise | RD range 0.06 to 0.14, p<0.05 in 1 of 2 trials | Low |
| Prevention/reduction of comorbid depression | ||||||
| 2; 68 | Medium; RCTs | Inconsistent | Direct | Imprecise | Mixed evidence | Insufficient |
| Prevention/reduction of comorbid pain | ||||||
| 1; 34 | Medium; RCT | NA, single study | Direct | Imprecise | P<0.05 | Insufficient |
CI = confidence interval; HSCL-25 = Hopkins Symptom Check List-25; NA = not applicable; NR = not reported; PDS = Posttraumatic Stress Diagnostic Scale; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial; SOMS= Screening for Somatoform Symptoms Scale; SRQ-20 = Self-Reporting Questionnaire
Table I-26Brief eclectic psychotherapy (BEP) compared with waitlist
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: various outcome measures | ||||||
| 1; 30a | Medium; RCTs | NA, single study | Direct | Imprecise | WMD −10.8, p=ns | Insufficient |
| Symptom Remission | ||||||
| 1; 30 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.13, p=ns | Insufficient |
| Loss of Diagnosis | ||||||
| 3; 96 | Medium; RCTs | Inconsistent | Direct | Imprecise | RD range 0.13 to 0.58b | Low |
| Prevention/reduction of comorbid depression | ||||||
| 3; 96 | Medium; RCTs | Inconsistent | Direct | Imprecise | P<0.05 in 3 of 3 studies | Low |
| Prevention/reduction of comorbid anxiety | ||||||
| 3; 96 | Medium; RCTs | Inconsistent | Direct | Imprecise | P<0.05 in 3 of 3 studies | Low |
| Return to work | ||||||
| 2; 66 | Medium; RCTs | Inconsistent | Direct | Imprecise | P<0.05 for 1 of 2 trialsc | Insufficient |
- a
The three trials used different outcome measures—two found small or medium effect sizes using the CAPS and SI-PTSD, respectively. The other did not report enough data to determine effect sizes.
- b
The three trials were consistent in the sense that they all found more subjects in the BEP group with loss of PTSD diagnosis compared with the WL group. However, the magnitude of the differences between groups was inconsistent
- c
One trials reported percentage of subjects on sick leave and the other reported percentage who had returned to work.
CI = confidence interval; mths = months; NA = not applicable; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Table I-27Brief eclectic psychotherapy (BEP) compared with EMDR
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: IES-R and SI-PTSD | ||||||
| 1; 140 | Medium; RCT | NA, single study | Direct | Imprecise | p=ns | Insufficient |
| Loss of Diagnosis | ||||||
| 1; 140 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.08 favoring EMDR, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: HADS depression | ||||||
| 1; 140 | Medium; RCT | NA, single study | Direct | Imprecise | p=ns | Insufficient |
| Prevention/reduction of comorbid anxiety: HADS anxiety | ||||||
| 1; 140 | Medium; RCT | NA, single study | Direct | Imprecise | p=ns | Insufficient |
CI = confidence interval; mths, months; NA = not applicable; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Table I-28Trauma affect regulation compared with waitlist
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 2; 173 | Medium; RCT | Consistent | Direct | Imprecise | Between-group mean difference of -17.4 and -2.7 in individual studies Both favored treatment (1 of 2 studies p<0.05) | low |
| Symptom Remission | ||||||
| 2; 173 | Medium; RCT | Inconsistent | Direct | Imprecise | RD range −0.11 to 0.21, effect sizes in opposite directions | Insufficient |
| Loss of Diagnosis | ||||||
| 2; 173 | Medium; RCT | Inconsistent | Direct | Imprecise | RD range 0.01 to 0.26 | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 93 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −4.1, p<0.05 | Insufficient |
| Prevention/reduction of comorbid anxiety | ||||||
| 1; 93 | Medium; RCT | NA, single study | Direct | Imprecise | p=ns | Insufficient |
BDI= Beck Depression Inventory; CI = confidence interval; mths, months; NA = not applicable; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Table I-29Interpersonal Therapy compared with Relaxation Therapy
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 72 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −6.3 favoring IPT, p<0.05 | Insufficient |
| Remission (CAPS<20) | ||||||
| 1; 72 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.04 favoring IPT | Insufficient |
| Prevention/reduction of comorbid depression: HAM-D | ||||||
| 1; 72 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −0.3, p=ns | Insufficient |
| Quality of Life: Quality of Life Enjoyment and Satisfaction Questionnaire | ||||||
| 1; 72 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −10.1 favoring IPT, p<0.05 | Insufficient |
| Function: Inventory of Interpersonal Problems Questionnaire | ||||||
| 1; 72 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −0.46 favoring IPT, p<0.05 | Insufficient |
CI = confidence interval; HAM-D= Hamilton Depression Rating Scale; NA = not applicable; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Table I-30Memory Specificity Training compared with control (no treatment)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: IES-R | ||||||
| 1; 24 | Medium; RCT | NA, single study | Direct | Imprecise | Greater reduction in scores among MEST group vs. controls (p<0.001)a | Insufficient |
| Prevention/Reduction of Comorbid Depression: BDI-II | ||||||
| 1; 24 | Medium; RCT | NA, single study | Direct | Imprecise | No difference between groups in score change from baseline (scores NR) | Insufficient |
- a
Baseline and followup scores are shown in figure only.
BDI-II = Beck depression inventory II questionnaire; CI = confidence interval; IES-R =Impact of Event Scale- Revised; NA = not applicable; NS= not significant; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Table I-31Structured Writing Therapy compared with usual care (substance abuse treatment)a
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: PDS | ||||||
| 1; 34 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −0.3 | Insufficient |
| Symptom Remission | ||||||
| 1; 34 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.12, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: reduction/remission of primary substance use diagnosis | ||||||
| 1; 34 | Medium; RCT | NA, single study | Direct | Imprecise | Days abstinent WMD 2.1 Substance use disorder Remission: (34.1; p=NS | Insufficient |
- a
Both groups received intensive treatment program for substance use disorders based on CBT and other components (e.g., individual therapy, social skills training, relapse prevention). No interventions related to PTSD symptoms were carried out during the usual substance abuse treatment program.
CI = confidence interval; NA = not applicable; NS= not significant; PDS = Posttraumatic Stress Diagnostic Scale; PTSD = post-traumatic stress disorder; RCT = randomized controlled trial
Key Question 2
Table I-32Placebo-controlled trials of alpha-blockers (prazosin)
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design/Quality | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 3; 117 | Medium; RCTs | Consistent | Direct | Imprecise | SMD -0.52 (95% CI, -0.90 to -0.14) | Low |
| Prevention/reduction of comorbid depression | ||||||
| 1; 40 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −5.0, p=ns | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-33Strength of evidence for divalproex compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 85 | Low; RCT | NA, single study | Direct | Imprecise | WMD −1.40, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: MADRS | ||||||
| 1; 85 | Low; RCT | NA, single study | Direct | Imprecise | WMD −0.6, p=ns | Insufficient |
| Prevention/reduction of comorbid anxiety: HAM-A | ||||||
| 1; 85 | Low; RCT | NA, single study | Direct | Imprecise | WMD 1.4, p=ns | Insufficient |
Table I-34Strength of evidence for tiagabine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 232 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −0.50, p-ns | Insufficient |
| Remission (CAPS less than 20) | ||||||
| 1; 232 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.02, p=ns | Insufficient |
| Disability/functional impairment: Sheehan Disability Scale | ||||||
| 1; 232 | Medium; RCT | NA, single study | Direct | Imprecise | WMD 0.4, p=ns | Insufficient |
Table I-35Strength of evidence for topiramate compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 3; 142 | Medium; RCT | Consistent | Direct | Imprecise | SMD ranged from -1.85 to -0.38 across individual studies | Low |
| Symptom Remission | ||||||
| 1; 40 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.21, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: BDI or HAM-D | ||||||
| 2; 75 | Medium; RCT | NA, single study | Direct | Imprecise | Both favored topiramate, p=ns in 2 of 2 trials | Insufficient |
| Prevention/reduction of comorbid anxiety: HAM-A | ||||||
| 1; 40 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −13.9, p=ns | Insufficient |
| Disability/functional impairment: Sheehan Disability Scale | ||||||
| 1; 40 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −4.8, p=ns | Insufficient |
Table I-36Olanzapine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design/Quality | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS and SIPS | ||||||
| CAPS 2; 47 All PTSD symptom scales 3; 62 | Medium; RCT | Consistent | Direct | Imprecise | SMD (CAPS) of -1.15 and -0.96 across individual studies. Both significantly favored treatment SMD ranged from -1.15 to 0.89 across individual studies. All studies favored treatment (2 of 3 studies p<0.05) | Low |
| Prevention/reduction of comorbid depression: CES-D | ||||||
| 1; 19 | Medium | NA, single study | Direct | Imprecise | WMD −0.37, p<0.05 | Insufficient |
| Disability/functional impairment: Sheehan | ||||||
| 2; 43 | Medium, RCT | Inconsistent | Direct | Imprecise | WMD range −4.2 to 0.3, 1 of 2 trials favored olanzapine, 1 of 2 trials favored placebo, p<0.05 for 1 of 2 trials | Insufficient |
| Return to work or return to active duty | ||||||
| 0; 0 | NA | NA | NA | NA | NA | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial; SIPS = Single Item PTSD Screeners.
Table I-37Risperidone compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design/Quality | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 4; 422 | Medium; RCTs | Inconsistent | Direct | Imprecise | SMD -0.26 (95% CI, -0.52 to -0.01) in 1 of 4 trials | Low |
| Prevention/reduction of comorbid depression: HAM-D | ||||||
| 1; 65 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −2.3, p=ns | Insufficient |
| Prevention/reduction of comorbid anxiety: HAM-A or PANSS | ||||||
| 2; 105 | Medium; RCT | Consistent | Direct | Imprecise | p<0.05 for 2 of 2 trials, favoring risperidone | Low |
CAPS = Clinician-Administered PTSD Scale; CI = confidence interval; HAM-A = Hamilton Anxiety Rating Scale; HAM-D = Hamilton Depression Rating Scale; NA = not applicable; PANSS = Positive and Negative Syndrome Scale; PTSD = posttraumatic stress disorder; RCT = randomized controlled trial; WMD = weighted mean difference.
Table I-38Citalopram compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI)a | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline in CAPS | ||||||
| 1; 35 | Medium; RCT | NA, single study | Direct | Imprecise | WMD 8.0, favoring placebo, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: BDI, mean change from baseline | ||||||
| 1; 35 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −0.47, p=ns | Insufficient |
- a
Data are from a single trial comparing citalopram, sertraline, and placebo.175
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial.
Table I-39Fluoxetine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline in CAPS | ||||||
| 4 (5 comparisons); 835 | Medium; RCTs | Consistent | Direct | Precise | SMD -0.28 (95% CI -0.42 to -0.14) | Moderate |
| Symptom Remission: Percent of subjects with CAPS less than 20 | ||||||
| 1; 52 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.03, p=ns | Insufficient |
| Loss of Diagnosis: percent of subjects no longer meeting criteria for PTSD diagnosis | ||||||
| 1; 59 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.14, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: mean change from baseline in MADRS | ||||||
| 3 (4 comparisons); 771 | Medium; RCTs | Consistent | Direct | Precise | SMD -0.20 (95% CI -0.40 to 0.00) | Low for no difference |
| Prevention/reduction of comorbid anxiety: mean change from baseline in HAM-A | ||||||
| 2 (3 comparisons); 712 | Medium; RCTs | Inconsistent | Direct | Imprecise | WMD range −3.0 to −1.5, both favored fluoxetine, p<0.05 in 1 of 2 trials | Low |
| Disability/functional impairment: mean change from baseline in SDS | ||||||
| 1; 54 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −5.8, p=ns | Insufficient |
- a
Data from subgroup analysis of subjects with combat-related PTSD in one trial (N=144 of the 301 from the main trial).173
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-40Paroxetine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline in CAPS | ||||||
| 2 (3 comparisons); 348 | Medium; RCTs | Consistent | Direct | Imprecise | SMD of -0.56 to -0.44 in individual studies Both studies favored treatment (2 of 2 studies p<0.05) | Moderate |
| Symptom Remission | ||||||
| 2; 348 | Medium; RCTs | Consistent | Direct | Imprecise | RD of 0.13 and 0.19 across 2 individual studies (1 of 2 studies p<0.05) | Moderate |
| Prevention/reduction of comorbid depression: mean change from baseline in MADRS | ||||||
| 2 (3 comparisons); 348 | Medium; RCTs | Consistent | Direct | Imprecise | SMD ranged from -0.60 to 0.34 across individual studies Both studies favored treatment (2 of 2 studies p<0.05) | Moderate |
| Disability/functional impairment: mean change from baseline in SDS | ||||||
| 2 (3 comparisons); 348 | Medium; RCTs | Consistent | Direct | Imprecise | WMD range −2.6 to −1.9, both favored paroxetine, p<0.05 in 2 of 2 trials (3 of 3 comparisons) | Moderate |
- a
Data are the best available evidence from a trial of paroxetine (N=323) that defined remission as a CAPS-2 total score less than 20 and found a significantly greater proportion of paroxetine-treated subjects achieved remission compared with placebo at week 12 (29.4% vs. 16.5%, p=0.008). The difference (12.9% difference between paroxetine and placebo) would translate to a number needed to treat of 7.8 to achieve one remission.65 The other trial contributing data for this outcome found similar percentages of subjects achieving remission (33% vs. 14%), but it was underpowered to detect anything but a very large difference for this outcome.174
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-41Sertraline compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: mean change from baseline in CAPS | ||||||
| 7; 1,085 | Medium; RCTs | Consistent | Direct | Precise | SMD -0.20 (95% CI: -0.36 to -0.04) | Low |
| Symptom Remission: Percent of subjects achieving CAPS-SX17 score less than 20 | ||||||
| 1; 352 | Medium; RCT | NA, single study | Direct | Imprecise | RD 4.4, p=NS | Insufficient |
| Prevention/reduction of comorbid depression: mean change from baseline in HAM-D | ||||||
| 7; 1,085 | Medium; RCTs | Inconsistent | Direct | Imprecise | SMD -0.14 (95% CI: -0.33 to 0.06) | Low for no difference |
| Prevention/reduction of comorbid anxiety: mean change from baseline in HAM-A | ||||||
| 2; 377 | Medium; RCTs | Inconsistent | Direct | Imprecise | Effects in opposite direction, p=ns for 2 of 2 trials | Insufficient |
| Quality of Life: mean change in Q-LES-Q | ||||||
| 2; 539 | Medium; RCTs | Consistent | Direct | Imprecise | WMD range −8.4 to −2.4, p<0.05 in 1 of 2 trials | Low |
| Disability/functional impairment: mean change from baseline in SDS | ||||||
| 1; 352 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −1.7, p=ns | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-42Venlafaxine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design/Quality | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: Change in CAPS | ||||||
| 2; 687 | Medium/RCT | Consistent | Direct | Precise | SMD of -0.35 and -0.26 for two individual studies | Moderate |
| Symptom Remission: defined by CAPS-Sx total score of 20 or less | ||||||
| 2; 687 | Medium/RCT | Consistent | Direct | Precise | RD of 0.12 and 0.15 across individual studies | Moderate |
| Prevention/reduction of comorbid depression: change in BDI | ||||||
| 2; 687 | Medium/RCT | Consistent | Direct | Precise | Between-group mean difference of -2.6 and 1.6 across individual studies. Both studies favored treatment. | Moderate |
| Prevention/reduction of comorbid anxiety | ||||||
| 0; 0 | NA | NA | NA | NA | NA | Insufficient |
| Quality of Life (change in Q-LES-Q-SF) | ||||||
| 2; 687 | Medium/RCT | Consistent (I2 0%) | Direct | Precise | WMD range 2.8 to 4.1, p<0.05 in 2 of 2 trials. | Moderate |
| Disability/functional impairment (change in SDS, and change in GAF) | ||||||
| 2; 687 | Medium/RCT | Consistent (I2 0%) | Direct | Precise | For SDS, WMD range −2.1 to −2.0, p<0.05 in 2 of 2 trials For GAF, WMD range 2.7 to 4.0, both trials favored venlafaxine, p<0.05 in 1 of 2 trials | Moderate |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-43Placebo-controlled trials of bupropion
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design/Quality | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS | ||||||
| 1; 30 | Medium; RCT | NA, Single Study | Direct | Imprecise | WMD 4.7, p=ns | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 30 | Medium; RCT | NA, single study | Direct | Imprecise | 0.4, p=ns | Insufficient |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-44Placebo-controlled trials of mirtazapine
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design/Quality | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: DTS | ||||||
| 1; 29 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −9.5, p=ns | Insufficient |
| PTSD Symptom Reduction: SPRINT | ||||||
| 1; 29 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −3.76, p=ns | Insufficient |
| PTSD Symptom Reduction: SIPS | ||||||
| 1; 29 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −10.8, p<0.05 | Insufficient |
| Prevention/reduction of comorbid depression: HADS-D | ||||||
| 1; 29 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −1.7, p=ns | Insufficient |
| Prevention/reduction of comorbid anxiety: HADS-A | ||||||
| 1; 29 | Medium; RCT | NA, single study | Direct | Imprecise | WMD −1.6, p<0.05 | Insufficient |
Table I-45Paroxetine + placebo compared with desipramine + placebo: Head-to-head trialsa
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS, mean change from baseline | ||||||
| 1; 88 | Medium; RCT | NA, single study | Direct | Imprecise | WMD, −3.2 favoring desipramine+placebo, p<0.05 | Low |
| Prevention/reduction of comorbid depression: HAM-D, mean change from baseline | ||||||
| 1; 88 | Medium; RCT | NA, single study | Direct | Imprecise | WMD, −1.3 favoring paroxetine+placebo, p=ns, | Low |
| Prevention/reduction of comorbid alcohol dependence: heavy drinking days and drinks per drinking day | ||||||
| 1; 88 | Medium; RCT | NA, single study | Direct | Imprecise | Greater reduction with desipramine, p<0.05 | Low |
- a
Data are from 1 trial of veterans with PTSD and comorbid alcohol dependence that compared Paroxetine + Naltrexone, Paroxetine + Placebo, Desiprimine + Naltrexone, and Desipramine + Placebo.
- b
Data NR for drinking outcomes; p=0.009 for percentage of heavy drinking days and p=0.027 for drinks per drinking day; shown in Figure only; magnitude of difference NR and difficult to read clearly from the Figure, all groups ended up less than 20 standard drinks per week (from baselines above 70 drinks per week), but it appears that the Desipramine groups ended up in the 0 to 10 drinks per week range and the paroxetine groups ended up in the 10-20 range at the 12 week endpoint.
CI = confidence interval; NA = not applicable; NR = not reported; RCT = randomized controlled trial
Table I-46Venlafaxine ER compared with sertraline: Head-to-head trials
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI)a | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS-SX17, mean change from baseline | ||||||
| 1; 538 | Medium; RCT | NA, single studyb | Direct | Precise | WMD range, −2.1 favoring sertraline, p=ns | Low for no difference |
| Symptom Remission: SX17 score of ≤20 at week 12 | ||||||
| 1; 538 | Medium; RCT | NA, single studyb | Direct | Precise | WMD, −5.9; p=ns, | Insufficient |
| Prevention/reduction of comorbid depression: HAM-D, mean change from baseline | ||||||
| 2; 745 | Medium; RCT | Consistent | Direct | Imprecise | WMD range −0.7 to −0.1, p=ns in 2 of 2 trials | Moderate for no difference |
| Quality of Life: Q-LES-Q or WHO-5, mean change | ||||||
| 2; 745 | Medium; RCT | Inconsistent | Direct | Imprecise | 1 trial favored venlafaxine, the other favored sertraline, p=ns in both trials | Low for no difference |
| Disability/functional impairment: SDS | ||||||
| 2; 745 | Medium; RCT | Inconsistent | Direct | Imprecise | 1 trial favored venlafaxine, the other favored sertraline, p=ns in both trials | Low for no difference |
- a
Data are from 1 multicenter trial comparing venlafaxine ER, sertraline, and placebo.69
- b
Although this is a single trial, it was a multicenter trial including 59 outpatient centers in the US. We considered this in our SOE grade.
CI = confidence interval; NA = not applicable; NR = not reported; p=placebo; RCT = randomized controlled trial; S = sertraline; V = venlafaxine ER
Table I-47Sertraline compared with citalopram: Head-to-head trials
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI)a | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS, mean change from baseline | ||||||
| 1; 58 | Medium; RCT | NA, single study | Direct | Imprecise | WMD, −11.1 favoring sertraline, p=ns | Insufficient |
| PTSD Symptom Reduction: IES, mean change from baseline | ||||||
| 1; 58 | Medium; RCT | NA, single study | Direct | Imprecise | WMD, −5.9; p=ns, | Insufficient |
| Prevention/reduction of comorbid depression: BDI | ||||||
| 1; 58 | Medium; RCT | NA, single study | Direct | Imprecise | WMD, −2.9; p=ns | Insufficient |
- a
Data are from 1 RCT comparing sertraline, citalopram, and placebo.175
C = citalopram; CI = confidence interval; NA = not applicable; NR = not reported; p=placebo; RCT = randomized controlled trial; S = sertraline
Key Question 3
Table I-48Head-to-head trials of psychological and pharmacological treatments: Fluoxetine compared with EMDR
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Mean, %, or Effect Size (ES) | High, Moderate, Low, Insufficient |
| PTSD Symptom Reduction: CAPS and PSS | Insufficient | |||||
| Fluoxetine vs. EMDR 1; 59 | Medium; RCT | Unknown (single study) | Direct | Imprecise | WMD −10.1 favoring fluoxetine, p=ns | Insufficient |
| Symptom Remission: | ||||||
| Fluoxetine vs. EMDR 1; 59 | Medium; RCT | Unknown (single study) | Direct | Imprecise | RD 0.15, p=ns | Insufficient |
| Loss of Diagnosis | ||||||
| Fluoxetine vs. EMDR 1; 59 (post) 1; 50 (f/up) | Medium; RCT | Unknown (single study) | Direct | Imprecise | RD 0.03 favoring EMDR, p=ns | Insufficient |
| Prevention/reduction of comorbid depression | ||||||
| Fluoxetine vs. EMDR 1; 59 (post) 1; 50 (f/up) | Medium; RCT | Unknown (single study) | Direct | Imprecise | WMD −1.9, p=ns favoring EMDR | Insufficient |
BDI = Beck Depression Inventory; CAPS = Clinician-Administered PTSD Scale – total; f/up, 6 month followup; NR = not reported; NS = non-significant; post = post-treatment; wk = week.
Key Question 4
Table I-49Strength of evidence for adverse events for fluoxetine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| Withdrawals due to Adverse Events | ||||||
| 3; 712 | Medium; RCTs | Inconsistent | Direct | Imprecise | One trial showed no difference, one trial favored fluoxetine, and one had two arms providing conflicting results; p=ns in 3 of 3 trials | Insufficient |
| Headaches | ||||||
| 3; 776 | Medium; RCTs | Inconsistent | Direct | Imprecise | One trial favored fluoxetine, two favored placebo; p=ns in 3 of 3 trials | Insufficient |
| Nausea | ||||||
| 2; 712 | Medium; RCTs | Consistent | Direct | Imprecise | Range 0.03 to 0.07 across two trials; p=ns in both trials | Low |
| Insomnia | ||||||
| 1; 301 | Medium; RCT | NA, single study | Direct | Imprecise | One study favored placebo, p=ns | Insufficient |
| Diarrhea | ||||||
| 1; 44 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.24, p<0.05 | Low |
| Somnolence | ||||||
| 1; 411 | Medium; RCT | NA, single study | Direct | Imprecise | RD range 0.04 to 0.06 (variation by dose), p-ns | Low |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-50Strength of evidence for adverse events for paroxetine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| Withdrawals due to Adverse Events | ||||||
| 3; 911 | Medium; RCTs | Consistent | Direct | Imprecise | All three studies favored placebo, p=ns in 3 of 3 studies | Insufficient |
| Nausea | ||||||
| 1; 323 | Medium; RCTs | NA, single study | Direct | Imprecise | RD 0.11, p<0.05a | Low |
| Dry mouth | ||||||
| 1; 323 | Medium; RCT | NA, single study | Direct | Imprecise | RD 0.10, p<0.05 | Low |
| Diarrhea | ||||||
| 1; 563 | Medium; RCT | NA, single study | Direct | Imprecise | Incidence of at least 10% and twice that of placebo64 | Insufficient |
| Somnolence | ||||||
| 1; 323 | Medium; RCTs | Consistent | Direct | Imprecise | RD 0.13, p<0.05a | Low |
| Drowsiness | ||||||
| 1; 25 | Medium; RCT | NA, single study | Direct | Imprecise | One study favored paroxetine, p=ns | Insufficient |
| Sexual adverse effects | ||||||
| 1; 563 | Medium; RCT | NA, single study | Direct | Imprecise | Incidence of at least 10% and twice that of placebo64 | Insufficient |
- a
Data are based on the only trial (N=323) reporting sufficient data to determine the risk difference.65 One additional trial (N=563) that provided narrative description reported that the most commonly reported adverse events associated with paroxetine use (with an incidence of at least 10% and twice that of placebo) were asthenia, diarrhea, abnormal ejaculation, impotence, nausea, and somnolence.64
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
Table I-51Strength of evidence for adverse events for venlafaxine compared with placebo
| Domains Pertaining to Strength of Evidence | Magnitude of Effect | Strength of Evidence | ||||
|---|---|---|---|---|---|---|
| Number of Studies; Number of Subjects | Risk of Bias; Design | Consistency | Directness | Precision | Summary Effect Size (95% CI) | High, Moderate, Low, Insufficient |
| Withdrawals due to Adverse Events | ||||||
| 2; 687 | Medium; RCTs | Inconsistent | Direct | Imprecise | One trial favored venlafaxine, one trial favored placebo; none were statistically significant | Insufficient |
| Headaches | ||||||
| 2; 687 | Medium; RCTs | Inconsistent | Direct | Imprecise | One trial favored venlafaxine, one trial favored placebo; none were statistically significant | Insufficient |
| Nausea | ||||||
| 2; 686 | Medium; RCTs | Consistent | Direct | Precise | Both trials favored placebo to a statistically significant degree | Moderate |
| Insomnia | ||||||
| 2; 687 | Medium; RCTs | Inconsistent | Direct | Imprecise | One trial favored venlafaxine, one trial favored placebo; none were statistically significant | Insufficient |
| Dry mouth | ||||||
| 2; 687 | Medium; RCTs | Consistent | Direct | Imprecise | RD range 0.04 to 0.08, p<0.05 in 1 of 2 trials | Low |
| Diarrhea | ||||||
| 1; 358 | Medium; RCTs | NA, single study | Direct | Imprecise | P=ns | Insufficient |
| Dizziness | ||||||
| 2; 687 | Medium; RCTs | Inconsistent | Direct | Imprecise | P=ns | Insufficient |
| Fatigue | ||||||
| 2; 687 | Medium; RCTs | Inconsistent | Direct | Imprecise | Both trials favored placebo, none to a statistically significant degree | Insufficient |
| Somnolence | ||||||
| 2; 687 | Medium; RCTs | Inconsistent | Direct | Imprecise | One trial favored venlafaxine, one trial favored placebo; none were statistically significant | Insufficient |
| Decreased appetite | ||||||
| 1; 358 | Medium; RCTs | NA, single study | Direct | Imprecise | One trial favored venlafaxine, but not to a statistically significant degree | Insufficient |
| Constipation | ||||||
| 2; 686 | Medium; RCTs | Consistent | Direct | Imprecise | RD range 0.02 to 0.09 across 2 trials, p<0.05 in 1 of 2 trials | Low |
CI = confidence interval; NA = not applicable; RCT = randomized controlled trial
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