Table 1.

Characteristics and outcome of reviewed enhancement studies

Author (year)	Cognitive enhancer	Population	Study design	Intervention	Outcome (CAPS)	Other outcome measure	Comments
De Kleine et al. 2012	DCS	Civilian, 79% women, mixed trauma, N=67	RCT; 50 mg DCS or placebo 60 minutes prior to (max) 9 prolonged exposure sessions	Prolonged exposure; imaginal exposure (30–45 minutes) & exposure in vivo; homework assignments; 1 psycho-education and 9 exposure sessions.	No significant time×group effects. Pretreatment: DCS: 61.8 Placebo: 73.8 Posttreatment (intent-to-treat; model means): DCS: 34.3 Placebo: 53.7	Self-report (PSS-SR): no time×group differences.
Litz et al. 2012	DCS	Veteran, male, N=26	RCT; 50 mg DCS or placebo 30 minutes prior to 4 exposure sessions	Brief exposure therapy; Imaginal exposure (50 minutes); 1 psycho-education, 4 exposure and 1 relapse prevention session.	Significant time×group effect, in favor of placebo. Pretreatment: DCS: 69.9 Placebo: 73.4 Posttreatment (intent-to-treat): DCS: 72.3 Placebo: 53.7	Self-report (PCL): significant time×group effect, in favor of placebo.
Bouso, Doblin, Farre, Alcazar, & Gomez-Jarabo, 2008	MDMA	Civilian, women, sexual assault, N=6	RCT; 50 mg MDMA, 75 mg MDMA or placebo prior to 1 experimental session	Confrontation with the traumatic event, discussion of narrative and new insights, experience-based (6 hours); 1 session			No results available
Mithoefer et al. 2011	MDMA	Civilian, 85% women, mixed trauma, N=20	RCT; 125 mg (+62.5 mg) MDMA or placebo prior to 2 exposure-based sessions	Relaxation, experience-based, introspection and discussion of experiences (8–10 hours); 2 introductory sessions, 2 MDMA/placebo enhanced sessions, 4 integration sessions after each enhanced session (8 in total).*	Significant time×group effect, in favor of MDMA. Pretreatment: MDMA: 79.2 Placebo: 79.6 Posttreatment: MDMA: 29.3 Placebo: 66.8	Self-report (IES-R): Significant time×group effect, in favor of MDMA.	Results were maintained at follow-up (Mithoefer et al., 2013)
Oehen et al. 2013	MDMA	Civilian, 83% women, mixed trauma, N=12	RCT; 125 mg+62.5 mg MDMA or active placebo 25+12.5 mg MDMA prior to 3 exposure-based sessions	Relaxation, experience- based, introspection and discussion of experiences (8–10 hours); 2 introductory sessions; 3 MDMA/active placebo enhanced sessions, 3 integration sessions after each enhanced session (9 in total).	No significant time×group effect. Pretreatment: MDMA: 66.4 Placebo: 63.4 Posttreatment: MDMA: 50.8 Placebo: 66.5	Self-report (IES-R): significant time×group effect, in favor of MDMA.
Brunet et al. 2008	Propranolol	Civilian, 52% women, mixed trauma, N=19	RCT; 40 mg short-acting+60 mg long-acting propranolol; immediately after 1 traumatic reactivation session	Traumatic memory reactivation; written description of index trauma (20 minutes); 1 session.	N/A	Physiological outcome: lower heart rate and skin conductance in response to trauma script in propranolol group.
Yehuda et al. 2010	Hydrocortisone	Veteran, male, N=2	Controlled case study; 30 mg hydrocortisone or placebo 30 minutes prior to 8 prolonged exposure sessions	Prolonged exposure; imaginal exposure (60 minutes) & exposure in vivo; homework assignments; 2 psycho-education and 8 exposure sessions.	Pretreatment: Hydrocortisone: 97.0 Placebo: 94.0 Posttreatment: Hydrocortisone: 43.0 Placebo: 52.0	Self-report (PSS-SR): more symptom decline in hydrocortisone treated than placebo treated patient.
Suris et al. 2010	Hydrocortisone	Veteran, male, N=20	RCT; 4mg/kg hydrocortisone or placebo immediately after 1 memory reactivation session	Traumatic memory reactivation; written account of 2 “worst” traumatic memories; 1 session.	N/A	Self-report (IES-R): lower avoidance/numbing symptoms in the hydrocortisone group compared to placebo.
Brunet et al. 2011	Propranolol	Civilian, 68% women, mixed trauma, N=28	Open label; 0.67 mg/kg short-acting+1 mg/kg long-acting propranolol (modal dose resp. 40 and 60 mg), 90 minutes prior to 6 sessions	Traumatic memory reactivation; reading aloud a written account of the index trauma (<15–20 minutes); 6 sessions.	Pretreatment: Propranolol: 71.8 Posttreatment: Propranolol: 45.8	Self-report (PCL): decline of self-reported PTSD symptoms.
	Propranolol	Civilian, 71% women, mixed trauma, N=7	Open label; 40 mg short-acting+80 mg long-acting (LA) propranolol, 90 minutes prior to 6 sessions	Traumatic memory reactivation; renarrating an oral account of the index trauma (<15–20 minutes); 6 sessions.	Pretreatment: Propranolol: 68.4 Posttreatment: Propranolol: 35.6
	Propranolol	Civilian, 71% women, disaster survivors, N=7 (treated)	Open label; 40 mg short-acting+80 mg LA propranolol 90 minutes prior to session 1, 80 mg LA propranolol 90 minutes prior to sessions 2–6	Traumatic memory reactivation; reading aloud a written account of the index trauma (<15–20 minutes); 6 sessions.	N/A	Self-report (PCL): more symptom decline in treated group than non-treated group.

^*Additional integration sessions were permitted if needed. Seven participants in the MDMA group received additional sessions (20 sessions in total), compared to 1 participant (1 session).

DCS: d-cycloserine; MDMA: ±3,4-methylenedioxymethamphetamine; RCT: Randomized clinical trial; CAPS: Clinician Administered PTSD Scale; N/A: not applicable; PSS-SR: posttraumatic Stress-Scale Self-Report; PCL: PTSD checklist; IES-R: Impact of event scale—revised form.