Table 1.
Characteristics of included studies.
| Methods |
Participants |
Outcomes |
Interventions |
Notes |
Risk of bias (low/unclear/high) |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SSRI plus therapy | Sequence generation | Allocation concealment | Blinding participants/personnel | Blinding outcome assessors | Incomplete outcome data | Free of selective reporting | Any other bias | ||||
| Study ID: Buhman 2018 Denmark Study type: Multicentre, pragmatic, randomised controlled trial with 2 × 2 factorial design Duration: 6 months |
N = 280 Mean age: 49 years Sex: 41% female Diagnosis: DSM-IV PTSD Predominant trauma type: Asylum experience Mean duration of Sx: 14.7 years |
HTQ HSCL-25 HRSD HRSA SCL-90 VAS SDS WHO-5 |
Group 1: Sertraline (25–200 mg, mean dose 132.1 mg) ± minaserin (10–30 mg, mean dose 20 mg) n = 71 Group 2: Sertraline (25–200 mg, mean dose 132.1 mg) ± minaserin (10–30 mg, mean dose 20 mg) plus therapy n = 71 Group 3: Therapy (16 sessions CBT over 6 months) n = 70 Group 4: Waiting list n = 68 |
54% of sessions were translated. 25% in therapy actually received exposure treatment. Additionally, 27% of the therapy group received another antidepressant. |
Low | Low | High | Low | Unclear | Low | High |
| Study ID: Hien 2015 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm, fixed dose Duration: 12 weeks |
N = 69 Mean age:unknown Sex: 81% female Diagnosis: DSM-IV-TR PTSD and AUD Predominant trauma type: CSA (46%) Mean duration of Sx: 14 years |
CAPS SCID-I TLFB |
Group 1: Sertraline (50–200 mg, mean dose) plus 12 weekly sessions of Safety Seeking (SS) therapy n = 32 Group 2: Placebo plus SS n = 37 |
Medication titrated over 2 weeks prior to therapy. | Low | Low | Low | Low | Low | Low | High |
| Study ID: Otto 2003 Cambodia Study type: Single centre, randomised, open label, FLEXIBLE DOSE Duration: 10 weeks of therapy. Unclear total treatment duration. |
N = 10 Mean age: 47.2 years Sex: 100% female Diagnosis: DSM-IV Predominant trauma type: survivors of Pol Pot regime Mean duration of Sx: 24 years |
CAPS ASI SCL-90-R |
Group 1: open label sertraline 25–200 mg plus group CBT n = 5 Group 2: sertraline 25–200 mg n = 5 |
Open label. | Unclear | High | High | High | High | Unclear | High |
| Study ID: Popiel 2015 Poland Study type: Single centre, randomised, double blind, three parallel arms Duration: 12 weeks |
N = 228 Mean age: 36.9 years Sex: unclear Diagnosis: DSM-IV-TR PTSD Predominant trauma type: Motor Vehicle Accident (100%) Mean duration of Sx: 17.7 months |
SCID-I PDS BDI-II |
Group 1: Prolonged exposure (PE) x 12 weekly sessions n = 114 Group 2: Paroxetine 20 mg x 12 weeks n = 57 Group 3: PE plus paroxetine 20 mg x 12 weeks n = 57 |
Unclear | High | High | Low | High | Unclear | Low | |
| Study ID: Rothbaum 2006 USA Study type: Multicentre, randomised, double blind, parallel arm, flexible dose Duration: 16 weeks |
N = 65 (88 completed 10 week open label) Mean age: 39.3 Sex: 64.6% female Diagnosis: DSM-IV PTSD Predominant trauma type: Sexual assault Mean duration of Sx: 8.1 years |
SIP BDI STAI-S |
Group 1: Sertraline 50–200 mg x 10 weeks open label followed by 5 weeks double blind sertraline plus 10 sessions of twice-weekly Prolonged exposure (PE) n = 34 Group 2: Sertraline 50–200 mg x 10 weeks open label followed by 5 weeks sertraline alone n = 31 |
Unclear | Unclear | High | High | Unclear | Unclear | High | |
| Study ID: Schneier 2012 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm Duration: 10 weeks |
N = 37 Mean age: 50.3 years Sex: 54% female Diagnosis: DSM-IV PTSD Predominant trauma type: WTC attacks Mean duration of Sx: 6.5 years |
CAPS HAMD QLESQ |
Group 1: Paroxetine (12.5–50 mg, mean dose 32.2 mg) plus 10 weekly sessions of PE n = 19 Group 2: Placebo plus 10 weekly sessions of PE n = 18 |
Unclear | Unclear | Low | Low | High | Low | High | |
| Study ID: Simon 2008 USA Study type: Multicentre, randomised, double blind, placebo controlled, parallel arm, flexible dose Duration: 10 weeks |
N = 68 Mean age: 46 years Sex: 56% female Diagnosis: DSM-IV PTSD Predominant trauma type: physical and sexual abuse (78%) Mean duration of Sx: unclear |
SPRINT CGI-S |
Group 1: paroxetine (12.5–62.5 mg) + Prolonged Exposure (PE) n = 9 Group 2: placebo + PE n = 14 |
Therapy course: - 8 sessions of open label PE (90–120 minutes) - non-responders randomised to treatment arms - 5 sessions of double blind PE plus paroxetine/placebo (90–120 minutes, fortnightly) x 10 weeks |
Unclear | Unclear | Unclear | Low | High | Unclear | High |
| Study ID: Sonne 2016 Denmark Study type: Single centre, randomised, pragmatic, parallel arm Duration: 6–7 months |
N = 207 Mean age: 43.7 years Sex: 40% female Diagnosis: ICD-10 PTSD Predominant trauma type: Refugee experience Mean duration of Sx: 41.6 years |
HTQ HAMD HAMA HSCL-25 SAS-SR CSS SDS WHO-5 SCL-90 GAF |
Group 1: venlafaxine (37.5–375 mg, mean dose 125.41 mg) (± mianserin) plus therapy n = 98 Group 2: sertraline (25–200 mg, mean dose 96.21 mg (± mianserin) plus therapy n = 109 |
Therapy = 16 sessions manualised flexible CBT (TF-CBT, ACT, stress Mx and MM) and social counselling | Low | Low | High | Low | Low | Low | High |
| DCS-assisted therapy | |||||||||||
| Study ID: De Kleine 2012 Netherlands Study type: Single centre, randomised, double blind, placebo controlled, parallel arm Duration: 10 weeks |
N = 67 Mean age: 38.3 years Sex: 80.6% female Diagnosis: DSM-IV PTSD Predominant trauma type: sexual abuse (52%) Mean duration of Sx: unknown |
CAPS BDI STAI |
Group 1: 50 mg DCS administered orally 1 hour prior to each face-to-face session of manualized PE n = 33 Group 2: administered orally 1 hour prior to each face-to-face session of manualized PE N = 34 |
No take-home DCS for homework. Concomitant psychotropics were allowed. |
Low | Low | Low | Low | Low | Low | Unclear |
| Study ID: Difede 2014 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm Duration: 12 weeks |
N = 25 Mean age: 45.8 years Sex: 24% female Diagnosis: DSM-IV PTSD Predominant trauma type: WTC attacks Mean duration of Sx: unclear |
CAPS SCID-MDD BDI-II STAXI-2 PCL |
Group 1: 12 weekly sessions of CBT including prolonged exposure enhanced by virtual reality (VRE)with 100 mg DCS 90 mins before sessions 2–11 n = 13 Group 2: 12 weekly sessions of CBT including prolonged exposure enhanced by virtual reality with placebo 90 mins before sessions 2–11 n = 12 |
Pharmacotherapy (on a stable dose for 2 months) allowed during therapy. | Unclear | Unclear | Low | Low | Low | High | High |
| Study ID: Litz 2012 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm Duration: 6 weeks |
N = 26 Mean age: 32 years Sex: 100~% male Diagnosis: DSM-IV PTSD Predominant trauma type: combat Mean duration of Sx: unclear |
CAPS BDI |
Group 1: 6 weekly exposure sessions with 50 mg DCS given 30 mins prior to sessions 2–5 n = 13 Group 2: 6 weekly exposure sessions with placebo given 30 mins prior to sessions 2–5 n = 13 |
Trial stopped before planned recruitment of 68 was reached. | Low | Low | Unclear | Low | Low | Unclear | High |
| Study ID: Rothbaum 2014 USA Study type: Randomised, double blind, placebo controlled, parallel arm Duration: 6 weeks |
N = 106 Mean age: 34.6 years Sex: 6% female Diagnosis: DSM-IV PTSD Predominant trauma type: combat (100%) Mean duration of Sx: unknown |
CAPS Startle response Salivary cortisol |
Group 1: 6 weekly 90 minute Virtual Reality Exposure (VRE) sessions with DCS 50 mg given 30 minutes prior to each session n = 53 Group 2: 6 weekly 90 minute VRE sessions with alprazolam given 30 minutes prior to each session n = 50 Group 3: 6 weekly 90 minute VRE sessions with placebo given 30 minutes prior to each session n = 53 |
56% were on a stable dose of psychotropic medications. | Unclear | Unclear | Unclear | Unclear | High | High | High |
| MDMA-assisted therapy | |||||||||||
| Study ID: Mithoefer 2010 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm, flexible dose Duration: 12 weeks |
N = 23 Mean age: 40.4 years Sex: 85% female Diagnosis: DSM-IV PTSD Predominant trauma type: crime related (95%) Mean duration of Sx: 19 years |
CAPS IES-R SCL-90-R RBANS PASAT RCFT |
Group 1: 12 therapy sessions with 125 mg MDMA given prior to sessions 3 and 7 n = 15 Group 2: 12 therapy sessions with placebo given prior to sessions 3 and 8 n = 8 |
MDMA-assisted therapy model includes male-female therapist dyad. Drug-assisted sessions last 6–8 hours, are non-directive and include music, eye mask and overnight stay. All participants were deemed to be treatment-resistant, although this was not clearly defined. Funded and managed by MAPS. |
Low | Low | High | Low | Low | Low | High |
| Study ID: Mithoefer 2018 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm, flexible dose Duration: 12 weeks |
N = 24 Mean age: 37.2 years Sex: 27% female Diagnosis: DSM-IV PTSD Predominant trauma type: service personnel Mean duration of Sx: 85.4 months |
CAPS-IV BDI-II PSQI PTGI NEO-PI-R DES-II GAF C-SSRS |
Group 1: 12 therapy sessions with 30 mg (active placebo) MDMA given prior to sessions 4 and 8 n = 7 Group 2: 12 therapy sessions with 75 mg MDMA given prior to sessions 4 and 8 n = 7 Group 3: 12 therapy sessions with 125 mg MDMA given prior to sessions 4 and 8 n = 12 |
MDMA-assisted therapy model includes male-female therapist dyad. Drug-assisted sessions last 6–8 hours, are non-directive and include music, eye mask and overnight stay. All participants were deemed to have chronic PTSD of at least 6 months duration or more. Modified ITT used; participants were included after one MDMA session. Funded and managed by MAPS. |
Low | Low | Low | Low | Low | Low | High |
| Study ID: Oehen 2013 Switzerland Study type: Single centre, randomised, double blind, placebo controlled, parallel arm, flexible dose Duration: 12 weeks |
N = 14 Mean age: 41.4 years Sex: 83% female Diagnosis: DSM-IV PTSD Predominant trauma type: CSA (50%) Mean duration of Sx: 18.3 years |
CAPS PDS |
Group 1: 12 therapy sessions with 25 mg (active placebo) MDMA given prior to sessions 3, 6 and 9 n = 5 Group 2: 12 therapy sessions with 125 mg (active placebo) MDMA given prior to sessions 3, 6 and 9 n = 9 |
MDMA-assisted therapy model includes male-female therapist dyad. Drug-assisted sessions last 6–8 hours, are non-directive and include music, eye mask and overnight stay. All participants were deemed to be treatment-resistant, defined as ‘having previously undergone at least 6 months of psychotherapy and 3 months of treatment with an SSRI’. Funded by MAPS. |
Unclear | Unclear | Low | Low | High | Low | High |
| Study ID: Ot’alora 2018 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm, flexible dose Duration: 12 weeks |
N = 28 Mean age: 42 years Sex: 67.9% female Diagnosis: DSM-IV PTSD Predominant trauma type: Mean duration of Sx: 29.4 years |
CAPS BDI-II PSQI DES-II |
Group 1: 12 therapy sessions with 100 mg MDMA given prior to sessions 4 and 8 n = 9 Group 2: 12 therapy sessions with 125 mg MDMA given prior to sessions 4 and 8 n = 13 Group3: 12 therapy sessions with 40 mg MDMA given prior to sessions 4 and 8 (active placebo) n = 6 |
MDMA-assisted therapy model includes male-female therapist dyad. Drug-assisted sessions last 6–8 hours, are non-directive and include music, eye mask and overnight stay. All participants were deemed to have chronic PTSD of at least 6 months duration or more. Modified ITT used; participants were included after one MDMA session plus one post-baseline assessment. Funded and managed by MAPS |
Low | Low | Low | Low | Low | Low | High |
| Other agents/approaches | |||||||||||
| Study ID: Brunet 2018 Canada Study type: Single centre, randomised, double blind, placebo controlled, parallel arm Duration: 6 weeks |
N = 61 Mean age:39.4 years Sex:58% female Diagnosis: DSM-IV-TR PTSD Predominant trauma type: physical and sexual (57%) Mean duration of Sx: unknown |
CAPS PCL-S |
Group 1: 6 weekly trauma memory reactivation sessions with propranolol (0.67 mg/kg short-acting plus 1 mg/kg long-acting preparations with food) n = 30 Group 2: 6 weekly trauma memory reactivation sessions with placebo n = 30 |
Brief intervention. First session 30 mins of written narrative. Subsequent sessions 10–20 minutes. | Low | Low | Low | Low | Low | Low | Low |
| Study ID: Tuerk 2018 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm, fixed dose Duration: 15 weeks |
N = 26 Mean age: 32.4 years Sex: 100% male Diagnosis: DSM-IV PTSD Predominant trauma type: combat Mean duration of Sx: unclear |
trauma-cued heart rate reactivity PCL-M BDI-II |
Group 1: Yohimbine 21.6 mg taken one hour prior to each Prolonged Exposure (PE) session n = 14 Group 2: Placebo taken one hour prior to each PE session n = 12 |
Low | Low | Low | Low | Low | Low | Unclear | |
| Study ID: Yehuda 2015 USA Study type: Single centre, randomised, double blind, placebo controlled, parallel arm, fixed dose Duration: 6 weeks |
N = 24 Mean age: 49.6 years Sex: unknown Diagnosis: DSM-IV PTSD Predominant trauma type: combat Mean duration of Sx: unknown |
CAPS PSS-SR BDI |
Group 1: 10 sessions of manualised prolonged exposure with 30 mg cortisol administered 20 minutes prior to sessions 3–10 n = 12 Group 2: 10 sessions of manualised prolonged exposure with placebo administered 20 minutes prior to sessions 3–10 n = 12 |
Insufficient data reported. | Low | Low | Low | Low | Unclear | Unclear | High |
| Study ID: Zoellner 2017 USA Study type: Duration: 6 weeks |
N = 42 Mean age: 37.5 years Sex: 100% female Diagnosis: DSM-IV-TR PTSD Predominant trauma type: physical assault (28.6%) Mean duration of Sx: |
PSS-I CGI SCID-IV PSS-SR QIDS-SR PTCI OSPAN SF-36 SUDS MEF |
Group 1: Six sessions of imaginal exposure (IE) plus 260 mg methylene blue(MB) administered post IE n = 15 Group 2: Six sessions of imaginal exposure (IE) plus placebo administered post IE n = 16 Group 3: Waiting list n = 11 |
Unclear | Unclear | Low | Unclear | Low | Low | Low | |