The concept that soldiers are tormented by the haunting memories of their wartime ordeals is a recurring theme that echoes through the ages, from the epic verses of Homer’s Iliad, the poetic prose of Shakespeare to the poignant pages of Tolstoy’s ‘war and peace’. Soldiers who were exposed to the trauma of war often experienced a range of symptoms, including anxiety, depression, nightmares, flashbacks, and physical symptoms such as shaking and trembling. Labeling these symptoms as the shell shock syndrome in military personnel during World War I was a significant milestone in the recognition of trauma and its effects on mental health. Initially, these symptoms were often dismissed as signs of weakness or cowardice, and soldiers were sometimes even accused of faking their symptoms to avoid combat. The recognition of shell shock and the subsequent establishment of PTSD as a diagnosis in 1980 (DSM-II) has spurred the creation of effective treatments that have helped many individuals attain recovery and lead satisfying lives. Still, PTSD in past and present members of the military tends to be a chronic condition with prevalence rates varying between 3 and 17% (1–3). Around 80% of those with a diagnosis of PTSD also meets criteria for another mental health condition such as depression, substance use disorder, or another anxiety disorder (4). While trauma-focused psychotherapy¹ may yield positive results for many individuals suffering from PTSD, veterans with PTSD benefit significantly less than non-military populations (5–8). After receiving trauma-focused psychotherapy for combat-related PTSD, approximately two-thirds of veterans still experience the lingering consequences of this disorder (7, 9). Another challenge arises as a considerable number of veterans prematurely end their treatment with dropout rates ranging from 25 to 48% (9, 10). Notwithstanding the advances in the field, it is increasingly evident that PTSD continues to be a complex and daunting condition for military personnel and veterans, posing formidable obstacles for traditional trauma-focused psychotherapies. Here, we examine the effectiveness of a novel treatment approach with the goal of mitigating the problem of treatment resistance and the high rates of dropout commonly observed in veterans.

Prior to delving into the details of our innovative treatment approach, we propose several plausible explanations that could clarify the relatively lower effectiveness of trauma-focused interventions in treating veterans with PTSD. Considering that PTSD is viewed as a disturbance of emotional memory (e.g., 11, 12), most psychotherapeutic approaches concentrate on exploring and addressing the individual’s recollection of the traumatic event or its meaning. Regardless of the specific therapeutic approach employed, they all involve revisiting the most distressing and agonizing memories associated with the traumatic experience. These memories, commonly referred to as “hotspot memories” and identified through the intrusive symptoms they elicit, serve as the basis for therapy (13–17). Successful reliving of these memories requires a focus on the sensory details and emotional responses that are integral to the memory (12, 18, 19). While perceptual memory reactivation may not be essential for reducing symptoms, it may facilitate a shift in meaning that ultimately predicts improved treatment outcomes (20). The general procedure to reactivate trauma memory is to instruct patients to imagine or describe the most disturbing traumatic situations, or the situation that is related to their hotspot memories. Yet, deliberately reliving the battlefield within a therapeutic context does not always guarantee easy access to the emotional intensity of the experience. We must not overlook the fact that military personnel undergo extensive training to equip them with the necessary skills to withstand the arduous physical and mental challenges inherent in their duties. Since emotions such as fear, anger, and sadness can have a significant impact on decision-making and performance in high-stress situations, military training often includes instruction on how to regulate and control their emotions while on duty. Hence, the efficacy of established trauma-focused therapies in evoking a deeply moving emotional response when recalling trauma memories in veterans might pose greater challenges compared to non-military individuals with PTSD. Pinpointing the per-symptom effectiveness of treatments in uncontrolled clinical settings in Israel indeed showed that only a small number of veterans (15.8%, n = 709) experienced minimal relief from symptoms of intrusive traumatic reexperiencing, while two other mnemonic symptoms, namely flashbacks and inability to recall an important aspect of the trauma, exhibited no response to treatment at all in this group of veterans (21). It is important to mention that not all veterans received trauma-focused therapy in this study. Nonetheless, the failure to effectively address these mnemonic symptoms in veterans may perpetuate other features of the disorder as well (21).

Another potential limitation is that current therapies were originally designed to address the excessive fear responses to trauma reminders, rather than the multifaceted emotions that may be present in military-related PTSD. Feelings of sadness, anger, shame, guilt, a sense of powerlessness, and betrayal are all common experiences that people may experience when being exposed to trauma (22). These feelings are particularly intense for members of the military who are often confronted with demanding ethical or moral decisions during their service (23). While decision-making is often likely to be consistent with their military codes of conduct, substantial levels of psychological distress can still be experienced when they perpetrate, witness or fail to prevent actions that run counter to their core moral or ethical values (24). This elevated state of distress is identified as ‘moral injury’, a condition closely linked to feelings of guilt, anger and shame (25, 26). As a result, individuals with combat-related trauma may not fully benefit from existing treatments, as their emotional needs remain unaddressed. When it comes to addressing the needs of military personnel dealing with PTSD, it’s also essential to consider the emotional toll that therapy can take on veterans. Most trauma-focused therapies require a prolonged course of treatment, which can be emotionally very taxing for military personnel. It is promising though that a recent study has shown a correlation between massed exposure therapy, which consists of delivering a full treatment program over a shorter duration, and a decrease in the number of veterans who discontinue the treatment (9). Hence, to truly develop more comprehensive and effective treatments for military-related PTSD, further research is necessary to better understand the emotional needs of veterans.

As an initial attempt to overcome the limitations of existing treatments for PTSD, we have developed a novel and concise intervention tailored to combat-related trauma. While most therapies rely on visual and verbal retrieval cues to access emotional memory, we believe that the use of multi-sensory and context-related stimuli as retrieval aids has been surprisingly underutilized. For instance, odors similar to the trauma context could be particularly powerful cues to spontaneously evoke autobiographical memories with a strong emotional resonance (27–31). One advantage of utilizing odors as retrieval cues is that the brain regions involved in olfaction have direct connections to the amygdala and entorhinal cortex (32, 33), both of which are involved in emotion processing and memory. To enhance access to emotional memory, we developed idiosyncratic virtual reality worlds that incorporate multi-sensory retrieval cues, including 3D visual, auditory, olfactory, and bodily information, tailored as much as possible to everyone’s personal experiences. After this brief memory reactivation procedure (i.e., 2 min), the focus was shifted toward the idiosyncratic memory representation of the veteran. On the basis of information provided in the intake we had formulated hypothesized stuck points that we tried to directly target in treatment. This part consisted of imaginal exposure combined with rescripting with the rationale that new perspectives on what happened during trauma are most effectively achieved by experiencing new views and emotions which were not possible at the time of the trauma (17, 34, 35). In a previous randomized-controlled trial in nonmilitary-related PTSD, we demonstrated that the addition of imagery rescripting to imaginary exposure led to a significant reduction of treatment dropouts, and better effects on guilt, anger and shame as compared to exposure alone (34).

Finally, a pivotal modification in the current intervention was to utilize the process of memory reconsolidation as an alternative means of inducing change. Most trauma-focused therapies are rooted on extinction learning with the notable limitation that it can only eliminate the fearful responding while leaving the original trauma memory intact (36, 37). As a consequence, the intact trauma memory may resurface thereby explaining the relatively high relapse rates even after initial treatment success (38, 39). In contrast, the hypothesis of memory reconsolidation suggests that it may be possible to target the trauma memory directly, with the promise of an instantaneous and more persistent alleviation of symptoms. Memory reconsolidation refers to the process that upon memory retrieval, items in long-term memory may temporarily return into a labile state requiring de novo protein synthesis in order to persist (40). This cascade of neurobiological processes offers a window of opportunity for targeting fear memories with amnestic agents. The crucial role of central noradrenergic signaling in the process cascade (41) suggests that the β-adrenergic blocker propranolol is a viable option for effectively interfering with memory reconsolidation in humans. Indeed, preclinical research has compellingly shown that β-adrenergic blockade during reconsolidation can disrupt fear memories in healthy individuals (e.g., (42); see for a review (43)) and in people with a fear of spiders ((44, 45); but see (46)). Even though these findings point to a revolutionary new treatment for emotional memory disorders, the success of reconsolidation interventions is not guaranteed (47). The effect of the intervention depends on whether memory retrieval effectively triggers reconsolidation. Only if the retrieval experience contains novel or unexpected information (i.e., prediction error), the memory engram will be destabilized (48, 49). While clinical research in patients with PTSD initially revealed a reduction in fear responding following a reconsolidation intervention (17, 50–52), these findings could not always be replicated in several follow-up trials ((53); see for a review (54)). It is worth highlighting that the design of these previous clinical trials raises several questions with respect to the necessary conditions for a reconsolidation intervention. The effectiveness of this intervention hinges on two key conditions: (i) the retrieval procedure should lead to the destabilization of the trauma memory, and (ii) the amnestic drug should interfere with the subsequent reconsolidation of that fear memory (43). In previous clinical trials, script-driven imagery was employed to reactivate traumatic memories, despite the fact that this method was explicitly designed to assess the passive retrieval of these memories, rather than their reconsolidation. Additionally, the timing of drug administration in these clinical trials (specifically, the use of long-acting propranolol after the reactivation of the traumatic memory) does not align with the reconsolidation hypothesis. We carried out a series of experiments aimed at exploring the optimal timing for administering propranolol. Our findings revealed a rather narrow temporal window, spanning less than four hours following memory reactivation, during which the β-adrenergic receptors assume a pivotal role in the reconsolidation of fear memories (47, 55).In summary, unlike traditional trauma-focused interventions that require multiple sessions with gradual and often temporary improvements, the memory reconsolidation intervention (i.e., Memrec) offers an unique approach to treating combat-related PTSD by providing a single, possibly effective treatment session that results in a sudden reduction in emotional symptoms. This innovative treatment approach also represents a departure from the conventional use of pharmaceutical agents to alleviate PTSD symptoms, as it involves a one-time administration of a very common drug (i.e., 40 mg propranolol HCl) after reliving and rescripting the combat-related trauma memory. In the current case series involving seven veterans we tested the effectiveness of Memrec for trauma in which we aimed to address the unparalleled complexities that are typically associated with treating combat-related PTSD.

Here, we present seven cases from an open-label pilot study of the reconsolidation intervention for veterans with PTSD. The patients were on the waiting list for trauma-focused treatment at ARQ Centrum ‘45, when offered the possibility of this intervention. All cases were treated by the first author (MK), who is a registered healthcare psychologist and an experienced cognitive behavioral therapist.

The findings of this small-scale case series cautiously suggest that Memrec holds promise for producing notable effects in just one or two treatment sessions. Clearly, four out of the seven veterans experienced a remarkable reduction in their PTSD symptoms. As for the remaining three veterans, two displayed improvements in their daily distress levels, notwithstanding the absence of a reduction on the PTSD symptom scale. Only one veteran did not exhibit any progress in his PTSD and distress symptoms, but this veteran (i.e., case 4) primarily struggled with depression rather than combat-related intrusive memories (see Figure 1H). Although the improvement in depression may appear less convincing based on these case series, three veterans showed a significant reduction in their depressive symptoms. Also, the quality of life saw a remarkable increase in most of the treated veterans (i.e., five out of the seven). It is important to note though that the long-term durability of these initial positive results remains uncertain, given that the last assessment occurred only three months after the treatment session. Nevertheless, the current findings demonstrate a general positive effect of this limited intervention, which is particularly noteworthy considering the complexity of symptoms experienced by this sample of veterans. In summary, there is reason to be optimistic for the treatment of combated-related PTSD, as it appears that there is much greater potential than commonly believed.

Certainly, we cannot conclusively attribute these effects to disrupting the process of memory reconsolidation (i.e., Memrec). Since we did not control for placebo or other trauma-focused treatments, nor for the well-known effects of a waiting list (67), the symptom reduction may also be due to other factors, including imagery rescripting, which is a fast-rising therapeutic technique yielding remarkably positive outcomes. Imagery rescripting is generally applied to treat symptoms associated with aversive mental images and is currently considered among the most effective treatments for patients with PTSD (68–71). Nevertheless, it is worth noting that the majority of these seven veterans seemed to be treatment resistant as they had already tried various trauma-focused treatments without any success, which at least suggests the presence of some specific active components in the current approach. The Memrec intervention was specifically designed to target trauma memories and it is therefore not surprising that one veteran who did not suffer from combat-related intrusions did not respond to the intervention. But also for the veterans who benefited from this intervention, it is evident that this treatment alone is not sufficient. Most participants (i.e., n = 6) were prior military service members with military-related PTSD, who had comorbid psychiatric conditions, had experienced multiple combat-related traumatic events, and had significant ongoing life stressors. They also grappled with profound relationship and familial challenges. Hence, there are so many other factors at play in post-war trauma survivors’ lives that Memrec or similar trauma-focused treatments should be offered as a module alongside existing treatment approaches.

Treating veterans with PTSD through memory-modifying approaches such as Memrec and Imagery Rescripting does, however, give rise to ethical considerations. These concerns encompass a range of potential issues, including the potential loss of autobiographical memories, the creation of false memories, and the unforeseen repercussions of modifying fear responses associated with traumatic memories (72). Our research findings indicate that the likelihood of losing explicit, declarative, or autobiographical memory through Memrec is very low. Individuals retained conscious awareness of previously acquired information even as the learned fear response was neutralized (20, 43). In contrast, overwhelming emotional memories can impede a patient’s ability to recall and make sense of their experiences (13). Consequently, reducing the emotional intensity of strongly encoded emotional memories through reconsolidation-based methods might paradoxically facilitate controlled recollection and integration into a coherent personal narrative, as observed in some veterans in our study (i.e., cases 5 and 6). Rather than inducing amnesia, the administration of propranolol after memory reactivation appears to primarily reduce the intense emotional impact associated with traumatic memories. Similarly, imagery rescripting may help patients reinterpret troubling past events, thereby lessening the impact of distressing memories, but it does not have the ability to erase or alter the original trauma memory (73). Another ethical concern is that some degree of fear and stress may serve a beneficial role in combat situations, preventing impulsive decisions and preparing the body for action. Hence, it may not be desirable to interfere with these emotional responses for military purposes. Nevertheless, experiments conducted in our laboratory have shown that even after mitigating learned fear through reconsolidation interventions, individuals can readily reacquire the same fear response when exposed to new threats (74). This demonstrates that military personnel who have undergone a memory-modifying intervention are not exempt from developing new emotional responses when reintroduced to real-life battlefield hazards. A clear strength of this study is its use of distinctive multi-sensoric retrieval cues to access the trauma-memory. Still, the 3D films alongside the smells were far from optimal as they could be more idiosyncratic. In addition to advance these more technological aspects of the intervention, for a next step we should systematically assess and explore the stuck points and explicitly formulate hypotheses on where and how to intervene. The current study is also limited by a small sample size, the absence of a control group, the absence of CAPS-5 assessments during the follow-up, the omission of multiple baseline measurements and the omission of long-term FU evaluations, which are typically included in more rigorously controlled case-series designs. The gold standard, naturally, aims to convey that a Randomized Controlled Trial (RCT) is the epitome of establishing the effectiveness of an intervention. When it comes to clinical practice, RCTs are not particularly beneficial in assessing the progress of individual clients. However, they can indeed prove useful in indicating which alternative treatments would be a promising starting point. On the other hand, psychotherapy studies are facing additional criticism for relying primarily on the average responses of large treatment groups, disregarding the variations within individuals that can influence the outcomes. In light of this criticism, researchers are now placing greater emphasis on the significance of individual treatment responses and the mechanisms of therapeutic change as the most effective means to improve efficacy (75). Single-case designs present an effective research methodology that systematically addresses individual differences over a period of time. This design significantly diminishes the likelihood of attributing changes solely to factors unrelated to the treatment and the conclusions drawn from such a study surpasses what can be derived from uncontrolled case studies (76). In the continued advancement of interventions for combat-related trauma, it is imperative for future research to build upon controlled case series and thoroughly examine the effectiveness of the intervention in addressing the wide array of symptoms commonly experienced by veterans.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving humans were approved by Medical Ethical Committee Amsterdam UMC. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

MK: Investigation, Writing – original draft. MS: Investigation, Writing – original draft.