Neither for nor against: reconsolidation's actual standing in the clinic
- The VA/DoD PTSD guideline (Version 4.0, June 2023) grades Recommendation 21 as "Neither for nor against | Reviewed, New-replaced": there is insufficient evidence to recommend for or against combining or augmenting psychotherapy or medication with any other psychotherapy or medication for PTSD. The Work Group's confidence in the quality of the evidence was very low.
- Inside that recommendation's discussion, the Work Group addresses the propranolol-with-trauma-memory-reactivation protocol directly and states it "is neither a combination nor augmentation treatment" – it fits none of the guideline's own categories. The Work Group records that the placebo-controlled trial "found the protocol was effective," then adds that because it was a single study it "was unable to recommend it because of serious imprecision."
- The trial in question is Brunet et al. 2018 (Am J Psychiatry 175(5):427-433): 60 adults with long-standing PTSD, propranolol or placebo 90 minutes before a brief weekly reactivation session over 6 weeks. Adjusted post-treatment CAPS group difference was 11.50 points. Within-group effect sizes were d=1.76 for propranolol and d=1.25 for placebo. The authors themselves called for replication with long-term follow-up in various trauma populations.
- The psychotherapy branch gets the same verdict. Recommendation 10 lists Reconsolidation of Traumatic Memories (RTM) among therapies with insufficient evidence for or against, based on two waitlist-controlled RCTs from the Lewis et al. (2020) meta-analysis: the guideline notes the data were positive but the evidence was judged very low quality.
Every few years a mechanism arrives looking ready for the clinic. Memory reconsolidation has looked ready for two decades. The clearest account of why it still has not arrived is not in a review article – it is in the fine print of the VA/DoD's PTSD guideline, and the reason is not that anyone refuted the mechanism.
The paragraph that decided it
Version 4.0 of the guideline files pharmacological add-ons under Recommendation 21: insufficient evidence to recommend for or against combination or augmentation, graded "Neither for nor against." Buried in its discussion is a paragraph that deserves far more attention than it gets.
Reviewing the Hoskins et al. (2021a) systematic review, the Work Group notes that the propranolol-with-reactivation protocol "is neither a combination nor augmentation treatment." The logic is exact: the drug is not being added to a working medication, and the brief reactivation session is not a psychotherapy in the guideline's sense. It is its own object, and the guideline has no shelf for it. The Work Group then records that the placebo-controlled trial "found the protocol was effective" – and immediately explains that because this was a single study, the review reported no meta-analytic finding for it, and the group "was unable to recommend it because of serious imprecision."
Read that sequence again. The protocol was not rejected. Its trial found the protocol was effective, it fit none of the available categories, and it was left unrecommendable on precision grounds.
The trial that could not carry a recommendation
The trial is Brunet 2018: 60 adults, six weekly sessions, propranolol or placebo 90 minutes before reactivation. The adjusted CAPS difference of 11.50 points is real and statistically significant. But the within-group numbers are the ones worth sitting with – d=1.76 for propranolol against d=1.25 for placebo. Placebo plus weekly reactivation produced a large effect by itself. The drug's contribution rests on top of a substantial non-specific one, in 60 people, at one centre, without long-term follow-up. The authors' own conclusion asked for exactly what the guideline later said was missing.
That is the translation gap in one line. Not a failed mechanism – an evidence base of one good trial being asked to do guideline-grade work.
Two doors, the same answer
Reconsolidation also knocked on the psychotherapy door and got the same reply. Recommendation 10 sweeps twenty-two individual psychotherapies into a single "neither for nor against" list, and Reconsolidation of Traumatic Memories sits on it: two waitlist-controlled trials, positive data, very low quality. Both branches of the reconsolidation family – pharmacological and psychotherapeutic – reached the same guideline and received the same verdict, for the same reason.
For practice, this makes the honest answer to a patient neither dismissal nor encouragement. The mechanism is solid in the laboratory. One good trial in 60 people supports a clinical protocol. The VA/DoD guideline neither recommends it nor recommends against it. The prevention literature is more sobering still: the same guideline records an RCT of early propranolol given in an emergency department that found no difference in the likelihood of developing PTSD versus placebo. For clinics already selling "memory reconsolidation therapy," Recommendation 21 is the document to read – not because it forbids anything, but because "neither for nor against" is a statement about evidence, and evidence is what a marketing claim is supposed to rest on.
The protocol was not rejected – its one trial found it effective, it fit none of the guideline's categories, and it was left unrecommendable on precision grounds.
The guideline is dated June 2023 and its evidence review closed earlier, so trials published since were not before the Work Group. A "neither for nor against" grade is a statement about the quantity and precision of evidence, not a finding that a treatment does not work.