Pharmacological Prevention of Posttraumatic Stress Disorder: A Systematic Review

Table 2

Prospective clinical trials of pharmacotherapy to prevent PTSD.

Study authors	Study population	Study design	Drug used	Outcome measure	Interval between trauma and initiation of drug therapy	Follow-up period	Results	Jadad score
(1) Pitman et al., 2002 [31]	Emergency department attenders (; 20 male) exposed to a traumatic event	Randomized, double-blind, placebo-controlled trial	Propranolol, 160 mg/day for 10 days; ( on propranolol, 23 on placebo)	PTSD diagnosis as per DSM-IV; PTSD symptoms as measured by CAPS	<6 hours	3 months	Nonsignificantly lower CAPS score in the propranolol group at 1 month; no difference in PTSD diagnosis across groups at 1 and 3 months	1
(2) Vaiva et al., 2003 [32]	Emergency department attenders (, 11 male) exposed to a traffic accident or physical assault	Nonrandomized open trial	Propranolol, 120 mg/day for 7 days ( on propranolol, 8 receiving treatment as usual)	PTSD diagnosis as per DSM-IV; PTSD symptoms as measured by Treatment Outcome PTSD Scale	9.5 ± 6 hours (range 2–20 hours)	2 months	Nonsignificantly lower PTSD diagnoses across groups (3/8 in controls, 1/11 in the propranolol group); significantly lower PTSD Scale symptoms in the propranolol group.	0
(3) Nugent et al., 2010 [33]	Pediatric trauma emergency department attenders (; 15 boys); the majority had traffic accidents	Randomized, double-blind, placebo-controlled trial	Propranolol, 40–80 mg/day ( on propranolol, 15 on placebo)	PTSD symptoms as measured by CAPS-CA	<12 hours	6 weeks	No significant difference in PTSD symptoms overall across groups; significantly increased PTSD symptoms in girls receiving propranolol	3
(4) Stein et al., 2007 [34]	Patients admitted to a surgical trauma centre (, 26 male); the majority had traffic accidents	Randomized, double-blind, placebo-controlled trial	Propranolol, 120 mg/day or gabapentin, 1200 mg/day for 14 days ( on propranolol, 14 on gabapentin, 17 on placebo)	PTSD diagnosis as per DSM-IV; PTSD symptoms as measured by PCL-C	<48 hours	8 months	No significant differences in PTSD diagnoses or PTSD symptoms across the three groups	4
(5) Schelling et al., 2001* [35]	Patients with septic shock admitted in a medical ICU (; only 20 available at follow-up; 8/20 male)	Randomized, double-blind, placebo-controlled trial	Hydrocortisone, 100 mg IV stat followed by 0.18 mg/kg/hr and then tapered ( on hydrocortisone, 11 on placebo)	PTSD diagnosis as per DSM-IV	Immediate^$	31 months (median; range 21–49 months)	Significantly lower frequency of PTSD in the hydrocortisone group (1/9 versus 7/11 placebo; )	2
(6) Schelling et al., 2004 [36]	Patients undergoing cardiac surgery (; 35 male)	Randomized, double-blind, placebo-controlled trial	Hydrocortisone, 100 mg IV stat followed by 10 mg/hr and then tapered ( on hydrocortisone, 22 on placebo)	PTSD symptoms as per PTSS-10	Immediate^%	6 months	Significantly lower PTSD symptom scores in the hydrocortisone group ()	3
(7) Zohar et al., 2011 [37]	25 adults experiencing a traumatic stressor (20 had traffic accidents; only 17 completed the study; 9/17 male)	Randomized, double-blind, placebo-controlled trial	Hydrocortisone, 100–140 mg as a single dose ( on hydrocortisone, 8 on placebo)	PTSD symptoms as per CAPS	<6 hours	3 months	Significantly lower PTSD symptom scores in the hydrocortisone group at 2 weeks and 3 months, but not at 1 month; trend to less frequent PTSD diagnosis at 3 months in the hydrocortisone group (0/9 versus 3/8 on placebo)	3
(8) Delahanty et al., 2013 [38]	Inpatients at a trauma unit (, 42 male); only 42 completed the study	Randomized, double-blind, placebo-controlled trial	Hydrocortisone, 40 mg/d orally for 10 days ( on hydrocortisone, 33 on placebo)	PTSD diagnosis and PTSD symptoms as per CAPS	<12 hours	3 months	Significantly lower PTSD symptom scores in the hydrocortisone group at 1 and 3 months (); less frequent PTSD diagnosis in the hydrocortisone group at 3 months, but not significant	3
(9) Stoddard et al., 2011 [39]	Children and adolescents with burns (age 6–20 years; )	Randomized, placebo-controlled, double-blind study	Sertraline, 25–150 mg/day for 24 weeks ( on sertraline, 9 on placebo)	PTSD symptoms as per parental report and self-report	Variable^&	24 weeks	Significantly greater decrease in parent-rated PTSD symptoms at 8, 12, and 24 weeks in the sertraline group; no difference in self-rated PTSD symptoms	2
(10) Shalev et al., 2012^# [40]	Adult survivors of trauma admitted to emergency services (; 107 male)	Randomized, double-blind, placebo-controlled study	Escitalopram, 20 mg/day for 12 weeks ( on escitalopram, 23 on placebo; 93 wait-list controls; 63 on prolonged exposure; 40 on cognitive therapy)	PTSD diagnosis and PTSD symptoms as per CAPS	29.35 ± 4.91 days	9 months	Similar rates of PTSD in the escitalopram and placebo groups at 5 months (61.9% versus 55.6% placebo) and 9 months (42.1% versus 47.1% placebo); no difference in PTSD symptoms	1
(11) Gelpin et al., 1996 [41]	Adult trauma survivors ()	Nonrandomized, controlled study	Benzodiazepines, either clonazepam (, mean dose 2.7 mg/day) or alprazolam (, mean dose 2.5 mg/day). 13 gender-matched trauma survivors formed the control group	PTSD diagnosis and PTSD symptoms as per CAPS	6.7 ± 5.8 days (range 2–18 days)	6 months	Higher rates of PTSD in the benzodiazepine group at 6 months (9/13 versus 3/13 in controls; )	0
(12) Mellman et al., 2002 [42]	Adult trauma centre admissions (; 14 male; 15 had traffic accidents)	Randomized, placebo-controlled study	Temazepam, 30 mg for 7 days ( on temazepam, 11 on placebo)	PTSD diagnosis and PTSD symptoms as per CAPS	14.3 ± 10 days	6 weeks	Nonsignificantly higher rates of PTSD in the benzodiazepine group at 6 weeks (6/11 versus 3/11 in controls; no significant effect of treatment on PTSD symptoms)	1
(13) Matsuoka et al., 2011 [43]	Patients presenting to an ICU with accidental injuries (; 11 completed the study)	Open-label study	PUFA capsules, 7/day for 12 weeks; no control group	PTSD diagnosis as per DSM-IV; PTSD symptoms as per CAPS	<240 hours (10 days)	12 weeks	Only 1/11 subjects developed PTSD at 4 weeks, and retained the diagnosis at 12 weeks.	1

PTSD: posttraumatic stress disorder, CAPS: clinician-assessed PTSD scale; CAPS-CA: clinician-assessed PTSD scale for children and adolescents, PCL-C: posttraumatic stress disorder checklist-civilian version, ICU: intensive care unit, and PTSS-10: posttraumatic 10 stress symptom inventory.
*Study initially conducted to study the haemodynamic effects of hydrocortisone in septic shock; PTSD assessed at long-term follow-up.
^#Study compared prolonged exposure (PE), cognitive therapy (CT), escitalopram and placebo.
^$Hydrocortisone given as a loading dose at ICU admission.
^%Hydrocortisone given as a loading dose during induction of anaesthesia.
^&This study included 12 children with acute burns and 14 admitted for reconstructive surgery, so time between trauma and sertraline initiation could not be computed.