No pills, more skills: The adverse effect of hormonal contraceptive use on exposure therapy benefit

Raeder, Friederike; Heidemann, Franziska; Schedlowski, Manfred; Margraf, Jürgen

doi:10.1016/j.jpsychires.2019.09.016

Cited by 23 publications

(13 citation statements)

References 41 publications

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“…The latter was evidenced on different outcome measures (i.e., subjective fear during the spider-BAT and self-reported spider fear). This is partially in line with previous observations [21,22], although we found this effect only in the stress-exposed group. The latter might be due to differences in the therapy protocol or sample characteristics used in the respective studies.…”

Section: Discussionsupporting

confidence: 93%

“…This is surprising, given that women are not only more likely to develop an anxiety disorder [18,19], but also exhibit greater severity and disability [20] relative to men. Nevertheless, we [21] and others [22] demonstrated that the responsiveness to exposure therapy is less pronounced in female spider-fearful participants taking OCs. It remains to be explored whether stress exerts a differential effect on exposure therapy efficacy in women based on OC use.…”

Section: Introductionmentioning

confidence: 48%

“…These factors have not been assessed systematically in previous therapy studies [3,4] or the studies were performed exclusively with women taking OC [38]. However, we and others showed that OC use diminishes the exposure-induced benefit in female participants with spider phobia [20,21].…”

Section: Discussionmentioning

confidence: 88%

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Effects of acute stress on exposure therapy outcome and generalization in women: considering the modulatory role of hormonal contraceptive use

Zlomuzica¹,

Raeder²,

Merz³

et al. 2021

Preprint

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The administration of glucocorticoids (GC) as an adjunct to exposure might represent a promising strategy to improve exposure therapy outcome in anxiety disorders (AD). The beneficial effects, however, might be sex-dependent and/or further modulated by hormonal factors (e.g., contraceptive usage in women). In the present study, we investigated whether acute stress before exposure therapy affects its efficacy in women using oral contraceptives (OC) relative to free-cycling (FC) women. In addition, possible effects of stress on generalization of therapy effects towards untreated stimuli were examined. Women with fears of spiders and cockroaches were randomly assigned to a stress (n=24) or no-stress (n=24) group prior to a standardized one-session exposure. Acute stress did not influence exposure-induced reduction in fear and avoidance of the treated stimuli (spiders). However, stress led to a less pronounced beneficial exposure outcome for treated stimuli in OC women relative to FC women. This effect occurred on the level of subjective fear and self-report questionnaires at post-treatment (24 hours after exposure) and follow-up (4 weeks after exposure). No effects of stress on generalization of therapy effects towards untreated stimuli (cockroaches) were found. Our findings suggest that OC usage diminishes the beneficial effects of stress on exposure therapy outcome seen in FC women. We present first clinical findings regarding the interaction of stress (and possibly GCs) and OC in exposure therapy of AD. OC intake in women constitutes a crucial factor to be considered in augmentation studies using stress and GCs.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 48%

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Effects of acute stress on exposure therapy outcome and generalization in women: considering the modulatory role of hormonal contraceptive use

Zlomuzica¹,

Raeder²,

Merz³

et al. 2021

Preprint

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“…By focusing on the contextual factor, which is a crucial element not only in renewal but also in other relapse phenomena (Bouton, 2014), these findings may help in developing more efficient interventions. In particular, our data suggest that the use of cortisol or stress should be promoted shortly before and avoided after extinction-based psychotherapy, taking into account possible factors that can affect cortisol concentrations (e.g., sex, sex hormones, and medication including hormonal contraceptives; see Kudielka et al, 2009;Merz and Wolf, 2017;Raeder et al, 2019). In cases wherein cortisol administration is not feasible, behavioral interventions might promote the desired moderate and timelimited cortisol response (Lass-Hennemann and Michael, 2014;Meir Drexler et al, 2017.…”

Section: Exposure Therapy and The Problem Of Relapsementioning

confidence: 92%

Stress modulation of fear and extinction in psychopathology and treatment

et al. 2020

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The glucocorticoid cortisol, a major player in the development of stress-related psychopathology, can also be used for the augmentation of extinction-based psychotherapies (e.g., exposure therapy). Substantial evidence supports its beneficial effects in the treatment of post-traumatic stress disorder and specific phobias. In this review, we first present the role of stress and cortisol in the development of maladaptive emotional memories. Then, we describe the mechanisms that may account for the cortisol-induced augmentation of exposure, namely, the enhancement of extinction memory consolidation and the reduction of the contextual dependency of the extinction memory. Finally, we discuss several considerations and limitations for the use of cortisol in psychotherapy, focusing on the possible adverse effects of cortisol in a reconsolidation-based (as opposed to extinction-based) intervention.

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“…We previously found differences between men and women in the effects of cortisol on fear memory reconsolidation (Meir Drexler et al, 2015, 2016). These differences may result from the influence of sex hormones on emotional learning and memory (e.g., during the female menstrual cycle or following hormonal contraceptives intake; Merz et al, 2018; Raeder et al, 2019; Velasco et al, 2019). For this reason, we limited our sample to men only.…”

Section: Methodsmentioning

confidence: 99%

Reactivation of the Unconditioned Stimulus Inhibits the Return of Fear Independent of Cortisol

Drexler

Merz

Lissek

et al. 2019

Front. Behav. Neurosci.

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Reconsolidation is the post-retrieval stabilization of memories, a time-limited process during which reactivated (i.e., retrieved) memories can be updated with new information, become stronger or weaker, depending on the specific treatment. We have previously shown that the stress hormone cortisol has an enhancing effect on the reconsolidation of fear memories in men. This effect was specific, i.e., limited to the conditioned stimulus (CS) that was reactivated, and did not generalize to other previously reinforced, but not reactivated CS. Based on these results, we suggested that cortisol plays a critical role in the continuous strengthening of reactivated emotional memories, contributing to their persistence and robustness. In the current study, we aimed to achieve a more generalized reconsolidation enhancement using an alternative reactivation method, i.e., by a low-intensity unconditioned stimulus (UCS) presentation instead of the more common unreinforced CS presentation. In previous studies, UCS reactivation was shown to lead to a more generalized reconsolidation effect. Therefore, we hypothesized that the combination of cortisol treatment and UCS reactivation would lead to an enhanced fear memory reconsolidation, which would generalize from previously reinforced CS to stimuli that resemble it. We tested 75 men in a 3-day fear conditioning paradigm: fear acquisition training on day 1; UCS reactivation/no reactivation and pharmacological treatment (20 mg hydrocortisone/placebo) on day 2; extinction training, reinstatement and test (of original and modified stimuli) on day 3. In contrast to our hypothesis, UCS reactivation prevented the return of fear [observed in skin conductance responses (SCR)] regardless of the pharmacological manipulation: while reinstatement to the original CS was found in the no-reactivation group, both reactivation groups (cortisol and placebo) showed no reinstatement. As the only methodological difference between our previous study and the current one was the reactivation method, we focus on UCS reactivation as the main explanation for these unexpected findings. We suggest that the robust prediction error generated by the UCS reactivation method (as opposed to CS reactivation), combined with the lower UCS intensity, has by itself weakened the emotional value of the UCS, thus preventing the return of fear to the CS that was associated with it. We call for future research to support these findings and to examine the potential of this reactivation method, or variations thereof, as a tool for therapeutic use.

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No pills, more skills: The adverse effect of hormonal contraceptive use on exposure therapy benefit

Cited by 23 publications

References 41 publications

Effects of acute stress on exposure therapy outcome and generalization in women: considering the modulatory role of hormonal contraceptive use

Effects of acute stress on exposure therapy outcome and generalization in women: considering the modulatory role of hormonal contraceptive use

Stress modulation of fear and extinction in psychopathology and treatment

Reactivation of the Unconditioned Stimulus Inhibits the Return of Fear Independent of Cortisol

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