Medications to prevent post-traumatic stress disorder (PTSD): a review of the evidence

Who may be interested in this review?

- People affected by PTSD and their families.
- Professionals working in adult mental health services.
- General practitioners.
- Charities that support victims of trauma or members of the armed forces.

Why is this review important?

PTSD is a condition experienced by some people after traumatic experiences such as warfare or domestic violence. People with PTSD experience symptoms of intense fear, helplessness and horror. Research suggests that changes in stress hormones in the brain may contribute to PTSD. Giving people medications which work in the brain soon after traumatic events may be able to prevent PTSD from developing.

Previous reviews have shown that talking therapy (cognitive behavioural therapy - CBT) is effective in preventing PTSD. This is the first review of medication as a preventative treatment for PTSD.

What questions does this review aim to answer?

- Is medication an effective preventative treatment for PTSD compared to placebo (dummy pills)?
- Is medication an acceptable treatment (do people stop medication due to side effects)?

Which studies were included in the review?

We searched databases to find all studies comparing medication with placebo for the prevention of PTSD, published up until February 2014. To be included in the review, studies had to be randomised controlled trials. Studies were included if they had adult participants aged over 18 who had experienced traumatic events but did not have a diagnosis of PTSD at the time of starting medication.

We included nine studies with a total of 345 participants in the review. Seven out of the nine studies had a high risk of bias due to problems with the research design.

What does the evidence from the review tell us?

There was moderate quality evidence that hydrocortisone (a steroid medication) prevented PTSD.

There was moderate quality evidence that hydrocortisone reduced the severity of PTSD symptoms.

There was no evidence that propranolol (a beta-blocker), escitalopram (a type of antidepressant), temazepam (a tranquillizer) or gabapentin (an anticonvulsant) prevented PTSD.

All medications were acceptable, with low numbers of people dropping out due to side effects; however not all studies provided information on this.

What should happen next?

The review authors do not feel there is sufficient evidence yet to recommend any medication as a preventative treatment for PTSD. The review authors recommend that future high quality research is needed to provide stronger evidence for the effectiveness of medications in preventing PTSD.

Authors' conclusions: 

There is moderate quality evidence for the efficacy of hydrocortisone for the prevention of PTSD development in adults. We found no evidence to support the efficacy of propranolol, escitalopram, temazepam and gabapentin in preventing PTSD onset. The findings, however, are based on a few small studies with multiple limitations. Further research is necessary in order to determine the efficacy of pharmacotherapy in preventing PTSD and to identify potential moderators of treatment effect.

Read the full abstract...
Background: 

Post-traumatic stress disorder (PTSD) is a debilitating disorder which, after a sufficient delay, may be diagnosed amongst individuals who respond with intense fear, helplessness or horror to traumatic events. There is some evidence that the use of pharmacological interventions immediately after exposure to trauma may reduce the risk of developing of PTSD.

Objectives: 

To assess the effects of pharmacological interventions for the prevention of PTSD in adults following exposure to a traumatic event.

Search strategy: 

We searched the Cochrane Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) (to 14 February 2014). This register contains relevant reports of randomised controlled trials from the following bibliographic databases: CENTRAL (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). We identified unpublished trials by searching the National Institute of Health (NIH) Reporter, the metaRegister of Controlled Trials database (mRCT) and the WHO International Clinical Trials Registry Platform (to December 2013). We scanned the reference lists of articles for additional studies. We placed no constraints on language and setting.

Selection criteria: 

We restricted studies to randomised controlled trials (RCTs) of pharmacological interventions compared with placebo for the prevention of PTSD in adults.

Data collection and analysis: 

Two authors (TA and JI) independently assessed trials for eligibility and inclusion based on the review selection criteria. We independently extracted sample, methodological, outcome and 'Risk of bias' data, as well as the number of side effects, from each trial and entered these into a customised data extraction form. We contacted investigators for missing information. We calculated summary statistics for continuous and dichotomous variables (if provided). We did not undertake subgroup analyses due to the small number of included studies.

Main results: 

We included nine short-term RCTs (duration 12 weeks or less) in the analysis (345 participants; age range 18 to 76 years). Participants were exposed to a variety of traumas, ranging from assault, traffic accidents and work accidents to cardiac surgery and septic shock. Seven studies were conducted at single centres. The seven RCTs included four hydrocortisone studies, three propranolol studies (of which one study had a third arm investigating gabapentin), and single trials of escitalopram and temazepam. Outcome assessment measures included the Clinician-Administered PTSD Scale (CAPS), the 36-Item Short-Form Health Survey (SF-36) and the Center for Epidemiological Studies – Depression Scale (CES-D).

In four trials with 165 participants there was moderate quality evidence for the efficacy of hydrocortisone in preventing the onset of PTSD (risk ratio (RR) 0.17; 95% confidence interval (CI) 0.05 to 0.56; P value = 0.004), indicating that between seven and 13 patients would need to be treated with this agent in order to prevent the onset of PTSD in one patient. There was low quality evidence for preventing the onset of PTSD in three trials with 118 participants treated with propranolol (RR 0.62; 95% CI 0.24 to 1.59; P value = 0.32). Drop-outs due to treatment-emergent side effects, where reported, were low for all of the agents tested. Three of the four RCTs of hydrocortisone reported that medication was more effective than placebo in reducing PTSD symptoms after a median of 4.5 months after the event. None of the single trials of escitalopram, temazepam and gabapentin demonstrated evidence that medication was superior to placebo in preventing the onset of PTSD.

Seven of the included RCTs were at a high risk of bias. Differential drop-outs between groups undermined the results of three studies, while one study failed to describe how the allocation of medication was concealed. Other forms of bias that might have influenced study results included possible confounding through group differences in concurrent medication and termination of the study based on treatment response.

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