Pharmacological memory modulation to augment trauma-focused psychotherapy for PTSD: a systematic review of randomised controlled trials.

Trauma-focused psychotherapy (tf-PT) is the first-line treatment for posttraumatic stress disorder (PTSD). Tf-PT focuses on processing and modulating trauma memories. Not all patients benefit, however, and there is room for improvement of efficacy. Pharmacologically augmenting trauma memory modulation in the context of tf-PT may help optimise treatment outcome. To systematically review effects of pharmacologically augmented memory modulation in the context of tf-PT for PTSD (PROSPERO preregistration ID: CRD42021230623). We conducted a systematic review of randomised controlled trials of psychotherapy treatment for PTSD. We included placebo-controlled studies that augmented at least one treatment session pharmacologically targeting memory extinction or reconsolidation. We calculated post-treatment between group (pharmacological augmentation vs placebo control) effect sizes of PTSD symptom severity. We included 13 RCTs. There was large heterogeneity in augmentation procedure and methodological quality. Four studies showed significantly greater PTSD symptom reduction in the pharmacological augmentation group (propranolol, hydrocortisone, dexamethasone, D-cycloserine) compared to placebo. Seven studies showed no significant effect of pharmacological augmentation compared to placebo (D-cycloserine, rapamycin, mifepristone, propranolol, mifepristone combined with D-cycloserine, methylene blue). Two studies showed significantly smaller PTSD symptom reduction in the pharmacological augmentation group (D-cycloserine, dexamethasone) compared to placebo. Results of pharmacological augmentation were mixed overall and heterogenous for the pharmacological agents tested in more than one study. Additional studies and replications are needed to identify which pharmacological agents work, in which combination and to identify patient groups that benefit most to tailor PTSD treatment.

Circadian influence on intrusive re-experiencing in trauma survivors' daily lives.

Background: The core clinical feature of posttraumatic stress disorder (PTSD) is recurrent re-experiencing in form of intrusive memories. While a great number of biological processes are regulated by sleep and internal biological clocks, the effect of 24-hour biological cycles, named circadian rhythm, has not been investigated in the context of intrusive memories. Objective: Here we examined effects of time of day on frequency and characteristics of intrusive re-experiencing. Methods: Fifty trauma survivors reported intrusive memories for 7 consecutive days using ecological momentary assessment in their daily life. We investigated (i) time-of-day dependent effects on frequency and distribution of intrusive re-experiencing in the overall sample as well as in PTSD versus non-PTSD and (ii) time-of-day dependent effects on the memory characteristics intrusiveness, vividness, nowness and fear. Results: Intrusive memories showed a curvilinear pattern that peaked at 2pm. Intrusive memories in the PTSD group showed a constant level of intrusive re-experiencing in the afternoon and evening, whereas a descending slope was present in the non-PTSD group. In PTSD, intrusive memories might thus be experienced in a more time-scattered fashion throughout the day, indicating chronodisruption. Intrusion characteristics did not follow this pattern. Conclusion: Although preliminary and based on a small sample size, these findings contribute to a better understanding of the everyday occurrence and characteristics of intrusive memories, and point to the added value of examining time-dependent effects, which can directly inform prevention and intervention science.

Antecedentes: La característica clínica central del trastorno de estrés postraumático (TEPT) es la re-experimentación recurrente en forma de recuerdos intrusivos. Si bien un gran número de procesos biológicos están regulados por el sueño y los relojes biológicos internos, el efecto de los ciclos biológicos de 24 horas, llamado ritmo circadiano, no ha sido investigado en el contexto de los recuerdos intrusivos.Objetivo: Aquí examinamos los efectos de la hora del día sobre la frecuencia y características de la re-experimentación intrusiva.Métodos: Cincuenta sobrevivientes de trauma reportaron recuerdos intrusivos por 7 días consecutivos usando la evaluación ecológica momentánea en su vida diaria. Investigamos (i) los efectos dependientes de la hora del día sobre la frecuencia y distribución de los recuerdos intrusivos en la muestra general, así como en TEPT versus no TEPT y (ii) los efectos dependientes de la hora del día sobre las características de la intrusividad de los recuerdos, vividez, momento presente y miedo.Resultados: Los recuerdos intrusivos mostraron un patrón curvilíneo que alcanzaba su punto máximo a las 2 pm. Los recuerdos intrusivos en el grupo con TEPT mostraron un nivel constante de re-experimentación intrusiva en la tarde y la noche, mientras que en el grupo sin TEPT se observó una pendiente descendiente. En el TEPT, los recuerdos intrusivos pueden experimentarse en una manera más dispersa en el tiempo a lo largo del día, lo que indica cronodisrupción. Las características de intrusión no siguieron este patrón.Conclusión: Aunque son preliminares y se basan en un tamaño de muestra pequeño, estos hallazgos contribuyen a una mayor comprensión de la ocurrencia cotidiana y las características de los recuerdos intrusivos y apuntan al valor agregado de examinar sus efectos dependientes del tiempo, que pueden informar directamente a la ciencia de la prevención e intervención.