Abstract
Post-traumatic stress disorder (PTSD) is a common mental disorder associated with significant distress and reduced functioning. Its occurrence after a severe traumatic event and association with characteristic neurobiological changes make PTSD a good candidate for pharmacological prevention and early treatment. The primary aim for this systematic review and meta-analysis was to assess whether pharmacological interventions when compared to placebo, or other pharmacological/psychosocial interventions resulted in a clinically significant reduction or prevention of symptoms, improved functioning or quality of life, presence of disorder, or adverse effects. A systematic search was undertaken to identify RCTs, which used early pharmacotherapy (within three months of a traumatic event) to prevent and treat PTSD and acute stress disorder (ASD) in children and adults. Using Cochrane Collaboration methodology, RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD severity. 19 RCTs met the inclusion criteria; 16 studies with adult participants and three with children. The methodological quality of most trials was low. Only hydrocortisone in adults was found to be superior to placebo (3 studies, n = 88, RR: 0.21 (CI 0.05 to 0.89)) although this was in populations with severe physical illness, raising concerns about generalisability. No significant effects were found for the other pharmacotherapies investigated (propranolol, oxytocin, gabapentin, fish oil (1470 mg DHA/147 mg EPA), fish oil (224 mg DHA/22.4 mg EPA), dexamethasone, escitalopram, imipramine and chloral hydrate). Hydrocortisone shows the most promise, of pharmacotherapies subjected to RCTs, as an emerging intervention in the prevention of PTSD within three months after trauma and should be a target for further investigation. The limited evidence for hydrocortisone and its adverse effects mean it cannot be recommended for routine use, but, it could be considered as a preventative intervention for people with severe physical illness or injury, shortly after a traumatic event, as long as there are no contraindications. More research is needed using larger, high quality RCTs to establish the most efficacious use of hydrocortisone in different populations and optimal dosing, dosing window and route. There is currently a lack of evidence to suggest that other pharmacological agents are likely to be effective.
Highlights
Post-traumatic stress disorder (PTSD) is a common mental disorder manifesting through symptoms of re-Astill Wright et al Translational Psychiatry (2019)9:334 predictor of PTSD4
No significant effects were found for the other pharmacotherapies investigated (propranolol, oxytocin, gabapentin, fish oil (1470 mg DHA/147 mg EPA), fish oil (224 mg DHA/22.4 mg EPA), dexamethasone, escitalopram, imipramine and chloral hydrate)
Selection criteria The inclusion criteria were: (a) any randomised controlled trials (RCTs); (b) investigating the effects of pharmacological intervention delivered within three months of the traumatic event; (c) when compared to placebo, pharmacological or psychosocial interventions; (d) in participants exposed to a traumatic event likely to meet the A criterion for DSM5 PTSD; and (e) PTSD or acute stress disorder (ASD) symptoms measured using one or more validated clinician administered or self-report outcome measures
Summary
Post-traumatic stress disorder (PTSD) is a common mental disorder manifesting through symptoms of re-Astill Wright et al Translational Psychiatry (2019)9:334 predictor of PTSD4. Post-traumatic stress disorder (PTSD) is a common mental disorder manifesting through symptoms of re-. Therapies to prevent early traumatic stress reactions developing into chronic PTSD, in high-risk individuals, are needed to alleviate this significant morbidity. While some psychological interventions to prevent the development of PTSD are ineffective[5] and others, such as psychological debriefing after trauma may even be harmful[6], there is evidence of benefit of trauma-focused cognitive behavioural therapy in treating individuals with acute traumatic stress symptoms[7] and preliminary work on prolonged exposure therapy in the immediate aftermath of trauma, has shown promise in the reduction of post-traumatic stress reactions[8]. The finding that memory consolidation appears vulnerable to disruption in the six hours after trauma[10], makes the shifts in neurobiological activity in these “golden hours”[11] and beyond a promising target for pharmacological intervention[12]
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