Why is this review important?
Post-traumatic stress disorder (PTSD) is a severe and disabling condition which may develop in people exposed to traumatic events. Such events can have long-lasting negative repercussions on the lives of those who have experienced them, as well as on the lives of loved ones.
Research has shown that there are some alterations in how the brain works in people with PTSD. Some researchers have thus proposed using medicines to target these alterations soon after a traumatic event, as a way to prevent the development of PTSD. However, the majority of people who experience a traumatic event will not develop PTSD. Therefore, medicines that can be given soon after exposure to a traumatic event must be carefully evaluated for their effectiveness, including balancing the risk of side effects against the risk of developing PTSD.
Who will be interested?
- People exposed to traumatic events and their family, friends, and loved ones
- Professionals working in mental health
- Professionals working in traumatology and emergency medicine
- People caring for victims of traumatic experiences and veterans of the armed forces
What questions did this review try to answer?
For people exposed to a traumatic event, whether or not they have psychological symptoms, are some medicines more effective than other medicines or placebo (dummy pills) in:
- reducing the severity of symptoms of PTSD?
- reducing the number of people stopping the medication because of side effects?
- reducing the probability of developing PTSD?
Which studies were included?
We searched scientific databases for studies in which participants were randomly assigned to a medicine with the aim of preventing PTSD and its symptoms or reducing severity. We included studies published up until November 2020. We selected studies in adults who had experienced any kind of traumatic event, and which provided treatment, regardless of whether or not the participants had psychological symptoms.
We included 13 studies, with a total of 2023 participants. One study alone contributed 1244 participants. The studies took place in different settings and involved people exposed to a wide range of traumatic events. Some studies took place in emergency departments and considered people whose trauma resulted from intentional harm or unintentional harm. Other studies focused on life-threatening illness as the source of trauma, including major surgeries or being admitted to intensive care units. The medicines most commonly given to participants in the studies included: hydrocortisone (which reduces the body's immune response), propranolol (used to treat heart problems and anxiety, amongst other conditions), and gabapentin (a medicine primarily used to treat seizures and nerve pain).
What did the evidence tell us?
We found four trials comparing hydrocortisone to placebo. These trials did not report how participants were doing at three months after a traumatic event, a time point that is usually useful to assess the evolution of PTSD symptoms.
We found very low-certainty evidence about propranolol compared to placebo three months after a traumatic event. This evidence does not tell us whether or not propranolol is more effective than placebo in reducing the severity of PTSD symptoms and the probability of developing PTSD. We did not find evidence on the probability of people stopping the medication because of side effects, quality of life, or functional disability (a measure of how much one’s life is limited by symptoms).
We found very low-certainty evidence about gabapentin compared to placebo three months after a traumatic event. This evidence does not tell us whether or not gabapentin is more effective than placebo in reducing the severity of PTSD symptoms and the probability of developing PTSD. We did not find evidence on the probability of people stopping the medication because of side effects, quality of life, or functional disability.
We found studies on additional medicines, for which information about the reduction of PTSD severity and the probability of people stopping the medication was either inconclusive or missing.
None of the included studies measured the functional disability of participants.
What should happen next?
The evidence we found does not support the use of any medicines for the prevention of PTSD in people exposed to a traumatic event, regardless of whether or not they have psychological symptoms. More higher quality studies involving more people are needed to draw conclusions about these treatments.
This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies. Future research might benefit from larger samples, better reporting of side effects and inclusion of quality of life and functioning measures.
Post-traumatic stress disorder (PTSD) is a severe and debilitating condition. Several pharmacological interventions have been proposed with the aim to prevent or mitigate it. These interventions should balance efficacy and tolerability, given that not all individuals exposed to a traumatic event will develop PTSD. There are different possible approaches to preventing PTSD; universal prevention is aimed at individuals at risk of developing PTSD on the basis of having been exposed to a traumatic event, irrespective of whether they are showing signs of psychological difficulties.
To assess the efficacy and acceptability of pharmacological interventions for universal prevention of PTSD in adults exposed to a traumatic event.
We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase, two other databases and two trials registers (November 2020). We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 13 November 2020.
We included randomised clinical trials on adults exposed to any kind of traumatic event. We considered comparisons of any medication with placebo or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy.
We used standard Cochrane methodological procedures. In a random-effects model, we analysed dichotomous data as risk ratios (RR) and number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD).
We included 13 studies which considered eight interventions (hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare enteral formula, Oxepa enteral formula and 5-hydroxytryptophan) and involved 2023 participants, with a single trial contributing 1244 participants. Eight studies enrolled participants from emergency departments or trauma centres or similar settings. Participants were exposed to a range of both intentional and unintentional traumatic events. Five studies considered participants in the context of intensive care units with traumatic events consisting of severe physical illness. Our concerns about risk of bias in the included studies were mostly due to high attrition and possible selective reporting. We could meta-analyse data for two comparisons: hydrocortisone versus placebo, but limited to secondary outcomes; and propranolol versus placebo. No study compared hydrocortisone to placebo at the primary endpoint of three months after the traumatic event.
The evidence on whether propranolol was more effective in reducing the severity of PTSD symptoms compared to placebo at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, serious inconsistency amongst the studies' results, and very serious imprecision of the estimate of effect (SMD -0.51, 95% confidence interval (CI) -1.61 to 0.59; I2 = 83%; 3 studies, 86 participants; very low-certainty evidence). No study provided data on dropout rates due to side effects at three months post-traumatic event. The evidence on whether propranolol was more effective than placebo in reducing the probability of experiencing PTSD at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, and very serious imprecision of the estimate of effect (RR 0.77, 95% CI 0.31 to 1.92; 3 studies, 88 participants; very low-certainty evidence). No study assessed functional disability or quality of life.
Only one study compared gabapentin to placebo at the primary endpoint of three months after the traumatic event, with inconclusive evidence in terms of both PTSD severity and probability of experiencing PTSD, because of imprecision of the effect estimate, serious risk of bias and serious imprecision (very low-certainty evidence). We found no data on dropout rates due to side effects, functional disability or quality of life.
For the remaining comparisons, the available data are inconclusive or missing in terms of PTSD severity reduction and dropout rates due to adverse events. No study assessed functional disability.