Taking hydrocortisone immediately after a traumatic event can help prevent PTSD

Taking hydrocortisone immediately after a traumatic event can help prevent PTSD

In an experimental study published in Translational Psychiatry, a single dose of hydrocortisone immediately after watching a stressful film was found to reduce intrusive memories related to the film compared to a placebo group in the following days. Voluntary memory is not affected. The effect was observed in both men and women.

Persistent, disturbing involuntary memories are a feature of many psychological disorders. In post-traumatic stress disorder, or PTSD, they are one of the most prominent features. PTSD develops after experiencing psychological trauma and is found in trauma survivors worldwide. In contrast to its wide distribution, there is a lack of capacity to treat it.

Researchers have studied ways to prevent the development of PTSD, and one promising approach focuses on preventing the consolidation of traumatic memories. Conceptually, if the disorder is primarily characterized by intrusive memories, preventing the formation of such memories could potentially prevent the disorder as a whole. But can the formation of these memories be prevented by the use of drugs that are introduced into the body?

“Uniquely among psychiatric disorders, there is a known cause of PTSD,” explained the study’s author Sunjeev Kamboj, Professor of Translational Clinical Psychology at University College London. “The cause is usually a traumatic (often life-threatening) event, which triggers a series of biological events in the brain that eventually lead to PTSD symptoms, including a so-called ‘re-experiencing’ cluster of symptoms that includes distressing involuntary memories and, in extreme cases, true flashbacks .”

“They occur because the biochemical processes involved in normal memory formation are ‘hijacked’ by a traumatic event, resulting in abnormally strong memories.” This abnormal strengthening occurs in the hours or days after the event, and as a result, we have a window of opportunity after the traumatic event to interfere with the formation of traumatic memories.”

“For example, it might be possible to use drugs to interrupt the biochemical processes involved in the formation of hyper-strong traumatic memories,” Kamboj explained. “Diverse lines of experimental and clinical evidence suggest that elevated levels of the ‘stress hormone’ cortisol may be associated with reduced PTSD. My lab is particularly interested in developing treatments that affect memory formation, so we wanted to know if giving participants cortisol (in the form of an oral medication, ‘hydrocortisone’) immediately after a mild simulated traumatic event in the lab would affect the emergence of later traumatic memories.”

“We were also very interested in the role of sex and sex hormones in PTSD, so we also looked at whether the effects of hydrocortisone would be influenced by baseline levels of estrogen and progesterone. By the way, it’s important to remember that women and men have these ‘female’ sex hormones in their systems!”

To test this, Kamboj and his colleagues conducted an experimental study on 120 healthy young volunteers, aged 18-35, recruited through online advertisements. The participants were randomly divided into two groups – an experimental group and a placebo group.

All participants had their blood pressure and heart rate measured and saliva samples taken before and after the experiment. They completed a set of psychological assessments of mental health and general psychological characteristics that included depression (Beck Depression Inventory), anxiety (Spielberger Trait Anxiety Inventory), dissociation (Dissociative Experiences Scale-II), sleep quality, and others.

Before and after the experimental treatment, the researchers assessed subjective performance (Positive and Negative Affect Scale, PABAS) and a range of subjective cognitive and physical sensations (Body Symptom Scale).

The experiment was conducted over 8 days. On the first day, after completing the described psychological and medical assessments, all participants watched a stressful film, intended as a proxy for the traumatic experience. When the film ended, the experimenters gave the experimental group capsules containing 30 mg of hydrocortisone, and the control group identical-looking capsules without active agents (placebo).

The experiment followed a double-blind procedure, which means that neither the experimenters, the people who administered the capsules and led the experiment, nor the study participants knew whether they were in the experimental or control group, that is, whether they were taking hydrocortisone or placebo capsules.

A 2-hour period followed to allow the drug to absorb, and participants were tasked with pressing a button on a wrist-mounted device whenever they had an intrusive memory related to the film. For the next 6 days, the participants were to fill in a memory diary in which they would record intrusive memories related to the film.

As expected, as the days passed, the intrusive memories related to the film became less frequent, but this reduction in frequency was faster in the group taking hydrocortisone capsules. While the occurrence of intrusive memories was the same on average on the first day in both groups, on the second day, as well as on all subsequent days, intrusive memories of the film were less frequent in the hydrocortisone group than in the placebo group.

However, the difference became large enough to be confirmed by statistical tests only from the fourth day onwards. Further analyzes confirmed the expectation that the frequency of intrusive memories declined faster over time in the hydrocortisone group.

“Although the findings need to be properly tested in larger clinical trials with recently traumatized individuals, it appears that hydrocortisone may help people ‘forget’ traumatic events more quickly if given very soon after the traumatic event,” Kamboj told PsyPost. “This will be difficult to test in clinical settings because traumatized people are usually treated in busy, chaotic emergency departments, and it is often understood that their physical needs take precedence over their mental health. ”

“However, the team in New York is doing this challenging work large clinical trial using a very high dose of hydrocortisone (6 times the dose we used in our study). The researchers expect to have preliminary results in the spring or summer of 2023.

The effects of hydrocortisone were the same for both sexes, but seemed to depend on the levels of the female sex hormones – estradiol and progesterone. “Men treated with hydrocortisone showed fewer intrusions with increasing estradiol levels, while women showed the opposite pattern,” the authors conclude, noting that a similar effect of progesterone was also present, but less pronounced.

“Although hydrocortisone on average accelerated the rate at which people forgot about the traumatic event, the total number of involuntary memories they had after hydrocortisone treatment appeared to depend on their circulating estrogen and progesterone levels,” Kamboj said.

“And the way these two hormones interacted with hydrocortisone appeared to be different in men and women. Overall, our findings suggest that whether hydrocortisone was beneficial (or even potentially harmful) depends on biological sex and salivary estrogen and progesterone levels. For example, men with high estrogen levels had the fewest involuntary traumatic memories after hydrocortisone.”

“Interestingly, women showed the opposite pattern – high estrogen levels in women were associated with more intrusive memories after hydrocortisone treatment,” the researcher continued. “Of course, these preliminary findings need to be replicated, but they suggest that hydrocortisone may not be a universally useful treatment for preventing PTSD, and we need to do more work to determine the factors responsible for making hydrocortisone an effective preventive treatment and whether there are conditions that potentially make it make it a harmful treatment in some individuals.”

The study makes an important contribution to finding new ways to prevent the negative psychological consequences of trauma. However, the authors note that a study design in which film is used to induce intrusions may not adequately “reflect the phenomenon seen following real-life trauma.”

“As noted above, the key question is whether hydrocortisone is effective in trauma victims,” ​​Kamboj explained. “It is unlikely that there is a simple answer to this question. For example, the clinical trial I mentioned tests a single (very high) dose of hydrocortisone, but we know from much previous experimental work that hydrocortisone’s effects are highly dose-dependent and that the dose-response relationship is not linear. ”

“I hope those researchers chose the ‘right’ dose to test, but if they don’t find an effect of hydrocortisone on preventing PTSD, we won’t know if it’s because the dose wasn’t quite right.”

The study, “Accelerated forgetting of trauma-like events in healthy men and women after a single dose of hydrocortisone“, by Vanessa E. Hennessy, Luzia Troebinger, George Iskandar, Ravi K. Das, and Sunjeev K. Kamboj.

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