121 Summary and General Discussion symptoms’ may be rather challenging in a disorder that has such a heterogeneity in its manifestation. I argue that this is particularly challenging for enhancement studies, that try to show an effect that goes on and above the effect of a relatively effective treatment that exposure is (Carpenter et al., 2018). In addition, there may be differential expectations and hence placebo-effects associated with different pharmacological enhancers. Another explanation for the mixed effects is that studies vary in the amount of enhanced sessions. Indeed for DCS-enhancement, it has been indicated that the number of enhanced sessions is related to its effects (Rosenfield et al., 2019; Smits et al., 2020). Does this mean that it is useless to conduct single-session administration studies? In the next section I will argue that as a proof of principle it may still be valuable to start with single-session enhancement, if alone to see if we can influence exposure-relevant mechanisms. The clinical assay: a quick win, fast fail? As mentioned above, I would like to reflect on the clinical assay design that we used in this dissertation to test the effects of testosterone as an enhancer for exposure treatment for SAD (see chapter 3, 4 and 5). This design originally described by Rodebaugh and colleagues (2013) is a brief experimental method consisting of two sessions. One session of exposure and one as an assessment session. It aims to test the potential of an intervention in a short and cost-effective manner prior to moving on to a large clinical trial. This method is referred to as a quick win fast fail approach as it tries to overcome the limitations of large clinical trials which are usually very expensive and time consuming, while they frequently fail to find clear effects. Although one session of exposure is insufficient as a full treatment, it does provide an elegant method for rapid assessment of the potential of different pharmacological enhancers like testosterone. Importantly, since it only consists of one dose of medication and two exposure sessions, it minimizes variance unrelated to the (pharmacological) enhancer. Rodebaugh and colleagues (2013) state that this method is an excellent complement to clinical trials. Within this dissertation we indeed experienced the advantages of this method as it allowed us to test the effects of testosterone on exposure in a restricted amount of time and we were successful in establishing reduction in social anxiety symptoms. Also, the burden to participants was as limited as possible. However, this method raised many new questions in our studies since we did not find clear support for the effects of testosterone neither did we find a full blown “fail.” Namely we observed interesting effects on in-session fear patterns that may be mechanistically relevant for exposure in the long run. As described in the discussion of chapter 4 we opt for future studies with ‘additional sessions plus testosterone’ to fully understand 6
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